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The Journal of Immunology, 2002, 169: 6673-6676.
Copyright © 2002 by The American Association of Immunologists

Cutting Edge

Cutting Edge: Differential Chemokine Production by Myeloid and Plasmacytoid Dendritic Cells1

Giuseppe Penna*, Marisa Vulcano{dagger}, Andrea Roncari*, Fabio Facchetti{ddagger}, Silvano Sozzani{dagger},§ and Luciano Adorini2,*

* BioXell and {dagger} Istituto Ricerche Farmacologiche "Mario Negri," Milano, Italy; and {ddagger} Anatomia Patologica II, Spedali Civili, and § Section of Immunology, Università degli Studi, Brescia, Italy


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
To examine the different roles of myeloid dendritic cells (M-DCs) and plasmacytoid dendritic cells (P-DCs) in the induction and regulation of immune response, we have studied chemokine secretion by freshly isolated DC subsets in response to bacterial, viral, and T cell-derived stimuli. M-DCs selectively produced very high levels of the homeostatic chemokines CC chemokine ligand (CCL)17 and CCL22, while P-DCs produced very little if any. In contrast, the proinflammatory chemokine CCL3 was secreted mostly by P-DCs, whereas CCL4 and CXC chemokine ligand 8 were produced by both subsets. The selective production of CCL17 and CCL22 by M-DCs but not P-DCs was confirmed in vivo by immunohistology on human reactive lymph node sections. The high production of CCR4 ligands by M-DCs suggests their capacity to selectively recruit at sites of inflammation T cells with regulatory properties or with a Th2 phenotype, whereas P-DCs, by preferentially secreting CCR1/CCR5 ligands, would mostly recruit effector T cells and, in particular, Th1-type cells.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Dendritic cells (DCs),3 a highly specialized APC system critical for the initiation of CD4+ T cell responses are heterogeneous in terms of origin, morphology, phenotype, and function (1, 2). Two distinct DC subsets were originally defined in the human blood based on the expression of CD11c. More recent work has characterized these two subsets as belonging to the myeloid or lymphoid lineage and, although different denominations have been used, they can be defined as myeloid DCs (M-DCs) and plasmacytoid DCs (P-DCs) (3). A cell population resembling human P-DCs has also been identified in the mouse (4).

M-DCs are characterized by a monocytic morphology, express myeloid markers like CD13 and CD33, the {beta}2 integrin CD11c, the stimulatory receptor Ig-like transcript 1 and low levels of the IL-3R {alpha}-chain CD123 (5). Conversely, P-DCs have a morphology resembling plasma cells, are devoid of myeloid markers, express high levels of CD4, CD62 ligand (CD62L) and CD123 (6, 7). M-DCs produce high levels of IL-12 (8), while P-DCs produce high levels of IFN-{alpha} (7, 9).

The proper localization of DCs in secondary lymphoid organs and their recruitment at sites of inflammation in response to chemotactic stimuli are critical for an optimal immune response. We have reported that, despite a similar expression and modulation of chemokine receptors, circulating P-DCs, in contrast to M-DCs, fail to migrate in response to inflammatory chemokines, while both subsets respond to lymph node homing chemokines following CD40 ligation (10). These different migration programs underscore the distinct lineage of these DC subsets and point to their divergent roles in the induction and regulation of the immune response.

To further define functional properties of M-DCs and P-DCs able to shape immune responses, in the present study we have analyzed their chemokine production in response to bacterial, viral, and T cell-derived stimuli. The results indicate a selective production of homeostatic chemokines, like CC chemokine ligand (CCL)17 and CCL22, by blood M-DCs. In contrast, P-DCs show a preferential production of proinflammatory chemokines, such as CCL3, pointing to a differential capacity of these two DC subsets to recruit discrete leukocyte populations at sites of inflammation.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Peripheral blood DC purification and culture

PBMCs were isolated from buffy coats by Ficoll gradient (Pharmacia Biotec, Uppsala, Sweden) and peripheral blood M-DCs and P-DCs were magnetically sorted with blood DC Ag (BDCA)-1 and BDCA-4 cell isolation kits (Miltenyi Biotec, Bergisch Gladbach, Germany), respectively, as described (11), to a purity of 95–98% in both cases. Blood M-DCs and P-DCs (2 x 104 cells/well) were cultured as described (10) in medium containing 1000 U/ml recombinant human GM-CSF (Mielogen; Schering-Plough, Kenilworth, NJ) and 10 ng/ml IL-4 (BD PharMingen, San Diego, CA) or 20 ng/ml IL-3 (BD PharMingen), respectively. Cells were stimulated with 1 µg/ml LPS (Escherichia coli 0111:B4; Sigma-Aldrich, St. Louis, MO), 1:5000 Staphylococcus aureus Cowans I (Pansorbin cells; Calbiochem, San Diego, CA), CD154-transfected J558L cells at a ratio of 4:1, 6 µg/ml CpG oligonucleotide 2006 (MGW Biotech, Ebersberg, Germany), and 20 ng of hemagglutinin/ml inactivated influenza virus strain A/Moscow/10/99 (a kind gift from Dr. T. De Magistris, Istituto Superiore di Sanità, Rome, Italy). After 24–72 h of culture, supernatants were collected and chemokine concentrations were measured by sandwich ELISA using Abs from R&D Systems (Minneapolis, MN).

Flow cytometric analysis

Flow cytometric analysis was performed as previously described (12), in the presence of 100 µg/ml mouse IgG, using the mAbs anti-CD1c (BDCA-1) FITC or PE, and anti-BDCA-2 FITC or PE (Miltenyi Biotec). Cells were analyzed with a FACScan flow cytometer (BD Biosciences, Mountain View, CA) using CellQuest software.

Chemotaxis of L1.2 hCCR4 cells

L1.2 cells transfected with human CCR4 were kindly provided by Dr. D. D’Ambrosio (BioXell, Milan, Italy). Chemotaxis assay was performed using 5-µm pore polyvinylpyrrolidone-free polycarbonate filters of 12-well transwell chambers (Corning Costar, Cambridge, MA). L1.2 hCCR4 cells were cultured for 16 h with 5 mM sodium butyrate, washed, and resuspended at a concentration of 1 x 106/ml in RPMI 1640 with 1% FCS. Supernatants from DC cultures or recombinant chemokines (0.6 ml) were added to the bottom chamber of the transwell and 0.1 ml of cell suspension was added to the top chamber. Transmigrated cells were recovered from the lower compartment of the transwell after a 3-h migration was performed at 37°C, and were quantified by trypan blue exclusion counting using light microscopy.

Immunohistology

CCL17 and CCL22 expression were evaluated on frozen sections from lymph nodes showing nonspecific reactive changes, using polyclonal goat anti-CCL17 Ab (Santa Cruz Biotechnology, Santa Cruz, CA) and a anti-CCL22 mAb kindly donated by Dr. P. Gray (ICOS, Bothell, WA). M-DCs and P-DCs were identified with anti-CD11c (BD Biosciences) and anti-CD123 (BD PharMingen), respectively. Immunohistochemistry was performed using the labeled streptavidin biotin system-HRP indirect immunoperoxidase technique (DAKO, Milan, Italy). Double immunofluorescence for CCL17 and CD11c was performed by applying anti-CCL17, followed by biotinylated rabbit anti-goat (Biogenex, San Ramon, CA) and Texas Red-conjugated streptavidin (Vector Laboratories, Burlingame, CA); after a 10-min incubation with normal goat serum, sections were treated with anti-CD11c and goat-anti-mouse IgG2b conjugated with FITC (Southern Biotechnology Associates, Birmingham, AL).


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Chemokine production by blood M-DCs and P-DCs

Peripheral blood DCs from healthy donors were magnetically purified based on the expression of BDCA-4, followed by B cell depletion and selection of BCDA-1+ cells, as described (11). As shown in Fig. 1Go, two discrete populations, both HLA-DR+ (data not shown) were obtained: expressing CD1c and negative for BDCA-2 expression (M-DCs), or expressing BDCA-2 (and BDCA-4, not shown) and negative for CD1c expression (P-DCs). Additional phenotypic analysis of the purified populations demonstrated that M-DCs were CD11c+, CD123low, CD62Llow, CD36low, and CD45 RAlow, whereas P-DCs were CD11c-, CD123high, CD62Lhigh, CD36high, and CD45 RAhigh (data not shown), confirming the subset assignment (7).



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  		FIGURE 1. Phenotype of enriched blood DC subsets. Phenotype of M-DCs and P-DCs purified with BDCA-1 and BDCA-4 isolation kits and stained for CD1c and BDCA-2 expression. Results are from a representative routine experiment.

 
M-DCs and P-DCs express different sets of Toll-like receptors (TLR), able to recognize distinct pathogen-associated molecular patterns, and thus respond to different stimuli. M-DCs have been found to express preferentially TLR1, 2, 4, 5, and 8, whereas P-DCs demonstrate a strong and selective expression of TLR7 and 9 (13, 14, 15). Because TLR4 is required for the response to LPS and TLR9 for the response to CpG oligonucleotides, the two DC subsets were expected to respond selectively to these stimuli. This is indeed the case also for chemokine production: P-DCs fail to respond to LPS and M-DCs to CpG, using as read-out the secretion of six different chemokines (Fig. 2Go). A striking result is the selective production by M-DCs of high levels of the homeostatic chemokines CCL22/monocyte-derived chemokine and CCL17/thymus and activation-regulated chemokine (TARC). A substantial level of these chemokines is produced constitutively by M-DCs, and it is strongly up-regulated by LPS and CD40 ligation. P-DCs fail to produce CCL17, either constitutively or following activation, after 24 h (Fig. 2Go) and at different time points up to 72 h (not shown) of culture. P-DCs also fail to produce CCL22 constitutively at 24 h (Fig. 2Go) and at any point tested up to 72 h (not shown) of culture, and secrete much lower levels than M-DCs after activation. Conversely, the proinflammatory chemokine CCL3/macrophage-inflammatory protein (MIP)-1{alpha} is mostly produced by P-DCs, whereas CCL4/MIP-1{beta} and CXC chemokine ligand (CXCL)8/IL-8 were produced at similar levels by both subsets. Neither P-DCs nor M-DCs produced CCL1/I-309, CCL2/monocyte chemoattractant protein-1, CCL5/RANTES, CCL18/pulmonary and activation-regulated chemokine, CCL19/MIP-3{beta}, or CXCL12/stromal cell-derived factor-11, and only minimal levels of CXCL10/IFN-{gamma}-inducible protein-10 were produced (Fig. 2Go). CCL20/MIP-3{alpha} was also not produced under any condition tested (data not shown). To ascertain whether the high levels of CCL22 and CCL17 produced by M-DCs were functional, culture supernatants were tested for their capacity to induce the migration of CCR4-transfected cells. Results in Fig. 3GoA demonstrate that CCR4-transfected cells migrate equally well in response to recombinant CCL22 and CCL17. Supernatants from cultures of M-DCs and P-DCs unstimulated or stimulated by CD40L-transfected cells showed constitutive production of CCL22 and CCL17 only by M-DCs, and this was further up-regulated by CD40 ligation (Fig. 3GoB), in agreement with the data reported in Fig. 2Go. The production pattern of CCR4 ligands was closely paralleled by migration of CCR4-transfected L1.2 cells (Fig. 3GoC), indicating that the chemokines produced are indeed functional. CCL22 and CCL17 transcripts in blood M-DCs and P-DCs have been also examined by RT-PCR. Although this approach is not quantitative, mRNAs for both chemokines were detected in M-DCs but were negligible in P-DCs (data not shown). These results parallel protein determinations obtained by ELISA, chemotaxis, and immunohistochemistry.



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  		FIGURE 2. Chemokine production by DC subsets in response to different stimuli. Magnetically purified M-DCs and P-DCs (2 x 104 cells/well) were cultured for 24 h in GM-CSF/IL-4 or IL-3, respectively, in the presence of S. aureus Cowans I (SAC), LPS, CpG, 2006, inactivated influenza virus (virus), or CD40L-transfected J558 cells (CD40L). Mean and SE of secreted chemokines (nanograms per milliliter) detected by two-site ELISA from 4–11 experiments are indicated.

 


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  		FIGURE 3. CCL22 and CCL17 produced in vitro are functional. Magnetically purified M-DCs and P-DCs (2 x 104 cells/well) were cultured for 24 h in GM-CSF/IL-4 or IL-3, respectively, with medium alone or containing CD40L-transfected J558 cells (CD40L). A, Migration of CCR4-transfected L1.2 cells to the indicated concentrations of recombinant CCL22 and CCL17. B, Chemokine production (mean ± SE from triplicate cultures) in the culture supernatant of unstimulated or CD40L-stimulated M-DCs and P-DCs. C, Migration (mean ± SE from triplicate cultures) of CCR4-transfected L1.2 cells in response to culture supernatants (diluted 1/10) from M-DCs and P-DCs. The data are from one representative experiment of two performed.

 
Selective production of CCL17 and CCL22 by M-DCs but not P-DCs in vivo

To confirm in vivo the selective production of CCL22 and CCL17 by M-DCs, their in situ production by reactive lymph node cells was examined by immunohistochemistry (Fig. 4Go). M-DCs, corresponding to interdigitating reticulum cells, and P-DCs were identified on frozen section from reactive lymph nodes with anti-CD11c and anti-CD123 mAbs, respectively. On subserial sections, staining with anti-CCL22 and anti-CCL17 showed cytoplasmic expression of both molecules by M-DCs. Fig. 4Go also shows a cell strongly positive for CCL22 production and with dendritic morphology forming a rosette with nearby lymphocytes. Double immunofluorescence revealed CD11c+CCL17+ cells with dendritic morphology. In contrast, P-DCs were uniformly negative for expression of CCL22 and CCL17. The endothelium of a high endothelial venule expressed CCL17, as previously reported in skin endothelial cells (16). Therefore, CCL22 and CCL17 are selectively produced by M-DCs, but not by P-DCs, also in vivo.



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  		FIGURE 4. Selective production of CCL22 and CCL17 by M-DCs but not P-DCs in vivo. Frozen sections from a reactive lymph node stained with anti-CCL22, anti-CCL17, anti-CD123, and double immunofluorescence for CCL17 and CD11c. M-DCs strongly express CCL22 and CCL17, the latter is obviously located in the cytoplasm (red) of a M-DC labeled on the cell membrane (green) by CD11c (upper panels). Serial sections of a large aggregate of P-DCs identified by anti-CD123 show that these cells do not express CCL22 and CCL17 (lower panels). Focal reactivity for CCL17 is recognizable on the endothelium of a high endothelial venule (arrow). Original magnification, from upper left to bottom right: x1100, x250, x1100, x180, x180, x180.

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
The present study demonstrates that chemokine production represents an additional level of diversity between human blood DC subsets. Production of the homeostatic chemokines CCL22 and CCL17 is a prerogative of M-DCs whereas P-DCs are quite efficient and selective producers of the inflammatory chemokine CCL3. The selective production of high levels of CCL22 by M-DCs is already apparent in unstimulated cells (over 1200 ng/106 cells/24 h) and is further enhanced (up to 6500 ng/106 cells/24 h) by bacterial and T cell-derived stimuli to levels much higher than those attained by monocyte-derived DCs (17). In contrast, much lower levels of CCL22 are produced by P-DCs. The production of CCL17 is even more strictly compartmentalized, with high levels produced by M-DCs and negligible ones by P-DCs. This strict compartmentalization is maintained also in DC subsets migrated to lymph nodes. Conversely, P-DCs, but not M-DCs produce relatively high levels of the proinflammatory chemokine CCL3 in response to bacterial, viral, and T cell-derived stimuli. The high production of CCR4 ligands by M-DCs suggests the capacity of this DC subset to selectively recruit at sites of inflammation T cells with a Th2 phenotype (18, 19) or CD4+CD25+ regulatory T cells (20, 21), whereas P-DCs, by preferentially secreting CCR1/CCR5 ligands, would mostly recruit effector T cells and, in particular, Th1-type cells (18, 22). However, P-DCs may also favor the induction of T cells with suppressive properties, as indicated by the generation of CD8+ regulatory T cells by CD40L-activated P-DCs (23). Mature M-DCs induce Th1 cell differentiation (8), but when immature they induce IL-10-producing CD4+ and CD8+ regulatory T cells (23, 24, 25). Our demonstration that blood and lymph node M-DCs produce chemokines able to recruit CD4+CD25+ T cells, as well as Th2 cells, indicates the capacity of this DC subset, unlike P-DCs, to attract T cells with regulatory properties. Interestingly, CCL22 produced by microglia has recently been proposed to regulate Th1-mediated inflammation of the CNS by facilitating the homing of Th2 and, possibly, regulatory T cells into the lesion site to counteract the inflammatory process (26).

Several chemokines, including CCL1, CCL2, CCL5, CCL18, CCL19, CCL20, and CXCL12 were not produced by either DC subset in response to any stimulus tested. In particular, CCL18, a chemokine reported to be produced in a constitutive manner by monocyte-derived DCs (27), was not detectably secreted by either blood DC subset, in both unstimulated and stimulated conditions. These results differ from a previous study where CCL18 was detected in activated CD11c+ blood DCs (28), and suggest that different stages of differentiation and/or of activation may modulate CCL18 production in DC subsets. Also CCL1, a chemokine able to recruit Th2 (29) and T regulatory (20, 21) cells was not produced under any condition tested.

Thus, similarly to what is observed in monocyte-derived DCs (17, 28), CCL17 and CCL22 are secreted in consistent levels by blood M-DCs and their production is strongly up-regulated following in vitro maturation. In contrast, neither circulating P-DCs nor P-DCs stimulated by CD40 ligation or by CpG secrete relevant levels of these two homeostatic chemokines. The migration behavior is also very different in the two cell types; circulating M-DCs migrate to several inflammatory chemokines in contrast to P-DCs responding only to the homeostatic chemokine CXCL12 (10). This would explain why P-DCs localize predominantly in secondary lymphoid organs, while M-DCs are rapidly recruited at sites of inflammation.

In conclusion, P-DCs produce preferentially proinflammatory chemokines but respond selectively to homeostatic ones whereas the reverse is true for M-DCs, highlighting not only the different migratory properties of these DC subsets but also their capacity to recruit different cell types at inflammation sites, and indicating a complementarity in their functional activity also in this respect.


   Acknowledgments
 
We thank Silvana Festa for expert technical assistance with immunohistochemical stainings.


   Footnotes
 
1 This work was supported in part by European Community Grants QLRT-1999-00276 (to S.S.) and QLRT-2000-02103 (to L.A.). Back

2 Address correspondence and reprint requests to Dr. Luciano Adorini, BioXell, Via Olgettina 58, I-20132 Milano, Italy. E-mail address: Luciano.Adorini{at}bioxell.com Back

3 Abbreviations used in this paper: DC, dendritic cell; M-DC, myeloid DC; P-DC, plasmacytoid DC; L, ligand; CCL, CC chemokine ligand; rh, recombinant human; BDCA, blood DC Ag; TLR, Toll-like receptor; MIP, macrophage-inflammatory protein; CXCL, CXC chemokine ligand. Back

Received for publication August 7, 2002. Accepted for publication October 10, 2002.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Banchereau, J., F. Briere, C. Caux, J. Davoust, S. Lebecque, Y. J. Liu, B. Pulendran, K. Palucka. 2000. Immunobiology of dendritic cells. Annu. Rev. Immunol. 18:767.[Medline]
  2. Reid, S. D., G. Penna, L. Adorini. 2000. The control of T cell responses by dendritic cell subsets. Curr. Opin. Immunol. 12:114.[Medline]
  3. Shortman, K., Y. J. Liu. 2002. Mouse and human dendritic cell subtypes. Nat. Rev. Immunol. 2:151.[Medline]
  4. Asselin-Paturel, C., A. Boonstra, M. Dalod, I. Durand, N. Yessaad, C. Dezutter-Dambuyant, A. Vicari, A. O’Garra, C. Biron, F. Briere, G. Trinchieri. 2001. Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology. Nat. Immunol. 2:1144.[Medline]
  5. Olweus, J., A. BitMansour, R. Warnke, P. A. Thompson, J. Carballido, L. J. Picker, F. Lund-Johansen. 1997. Dendritic cell ontogeny: a human dendritic cell lineage of myeloid origin. Proc. Natl. Acad. Sci. USA 94:12551.[Abstract/Free Full Text]
  6. Grouard, G., M. C. Rissoan, L. Filgueira, I. Durand, J. Banchereau, Y. J. Liu. 1997. The enigmatic plasmacytoid T cells develop into dendritic cells with interleukin (IL)-3 and CD40-ligand. J. Exp. Med. 185:1101.[Abstract/Free Full Text]
  7. Cella, M., D. Jarrossay, F. Facchetti, O. Alebardi, H. Nakajima, A. Lanzavecchia, M. Colonna. 1999. Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat. Med. 5:919.[Medline]
  8. Rissoan, M. C., V. Soumelis, N. Kadowaki, G. Grouard, F. Briere, R. de Waal Malefyt, Y. J. Liu. 1999. Reciprocal control of T helper cell and dendritic cell differentiation. Science 283:1183.[Abstract/Free Full Text]
  9. Siegal, F. P., N. Kadowaki, M. Shodell, P. A. Fitzgerald-Bocarsly, K. Shah, S. Ho, S. Antonenko, Y. J. Liu. 1999. The nature of the principal type 1 interferon-producing cells in human blood. Science 284:1835.[Abstract/Free Full Text]
  10. Penna, G., S. Sozzani, L. Adorini. 2001. Cutting edge: selective usage of chemokine receptors by plasmacytoid dendritic cells. J. Immunol. 167:1862.[Abstract/Free Full Text]
  11. Dzionek, A., A. Fuchs, P. Schmidt, S. Cremer, M. Zysk, S. Miltenyi, D. W. Buck, J. Schmitz. 2000. BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood. J. Immunol. 165:6037.[Abstract/Free Full Text]
  12. Penna, G., L. Adorini. 2000. 1 {alpha},25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J. Immunol. 164:2405.[Abstract/Free Full Text]
  13. Kadowaki, N., S. Ho, S. Antonenko, R. W. Malefyt, R. A. Kastelein, F. Bazan, Y. J. Liu. 2001. Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J. Exp. Med. 194:863.[Abstract/Free Full Text]
  14. Jarrossay, D., G. Napolitani, M. Colonna, F. Sallusto, A. Lanzavecchia. 2001. Specialization and complementarity in microbial molecule recognition by human myeloid and plasmacytoid dendritic cells. Eur. J. Immunol. 31:3388.[Medline]
  15. Hornung, V., S. Rothenfusser, S. Britsch, A. Krug, B. Jahrsdorfer, T. Giese, S. Endres, G. Hartmann. 2002. Quantitative expression of toll-like receptor 1–10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J. Immunol. 168:4531.[Abstract/Free Full Text]
  16. Campbell, J. J., G. Haraldsen, J. Pan, J. Rottman, S. Qin, P. Ponath, D. P. Andrew, R. Warnke, N. Ruffing, N. Kassam, et al 1999. The chemokine receptor CCR4 in vascular recognition by cutaneous but not intestinal memory T cells. Nature 400:776.[Medline]
  17. Vulcano, M., C. Albanesi, A. Stoppacciaro, R. Bagnati, G. D’Amico, S. Struyf, P. Transidico, R. Bonecchi, A. Del Prete, P. Allavena, et al 2001. Dendritic cells as a major source of macrophage-derived chemokine/CCL22 in vitro and in vivo. Eur. J. Immunol. 31:812.[Medline]
  18. Bonecchi, R., G. Bianchi, P. P. Bordignon, D. D’Ambrosio, R. Lang, A. Borsatti, S. Sozzani, P. Allavena, P. A. Gray, A. Mantovani, F. Sinigaglia. 1998. Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J. Exp. Med. 187:129.[Abstract/Free Full Text]
  19. Andrew, D. P., M. S. Chang, J. McNinch, S. T. Wathen, M. Rihanek, J. Tseng, J. P. Spellberg, C. G. Elias 3rd. 1998. STCP-1 (MDC) CC chemokine acts specifically on chronically activated Th2 lymphocytes and is produced by monocytes on stimulation with Th2 cytokines IL-4 and IL-13. J. Immunol. 161:5027.[Abstract/Free Full Text]
  20. Sebastiani, S., P. Allavena, C. Albanesi, F. Nasorri, G. Bianchi, C. Traidl, S. Sozzani, G. Girolomoni, A. Cavani. 2001. Chemokine receptor expression and function in CD4+ T lymphocytes with regulatory activity. J. Immunol. 166:996.[Abstract/Free Full Text]
  21. Iellem, A., M. Mariani, R. Lang, H. Recalde, P. Panina-Bordignon, F. Sinigaglia, D. D’Ambrosio. 2001. Unique chemotactic response profile and specific expression of chemokine receptors CCR4 and CCR8 by CD4+CD25+ regulatory T cells. J. Exp. Med. 194:847.[Abstract/Free Full Text]
  22. Loetscher, P., M. Uguccioni, L. Bordoli, M. Baggiolini, B. Moser, C. Chizzolini, J. M. Dayer. 1998. CCR5 is characteristic of Th1 lymphocytes. Nature 391:344.[Medline]
  23. Gilliet, M., Y. J. Liu. 2002. Generation of human CD8 T regulatory cells by CD40 ligand-activated plasmacytoid dendritic cells. J. Exp. Med. 195:695.[Abstract/Free Full Text]
  24. Jonuleit, H., E. Schmitt, G. Schuler, J. Knop, A. H. Enk. 2000. Induction of interleukin 10-producing, nonproliferating CD4+ T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J. Exp. Med. 192:1213.[Abstract/Free Full Text]
  25. Dhodapkar, M. V., R. M. Steinman, J. Krasovsky, C. Munz, N. Bhardwaj. 2001. Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J. Exp. Med. 193:233.[Abstract/Free Full Text]
  26. Columba-Cabezas, S., B. Serafini, E. Ambrosini, M. Sanchez, G. Penna, L. Adorini, F. Aloisi. 2002. Induction of macrophage-derived chemokine/CCL22 expression in experimental autoimmune encephalomyelitis and cultured microglia: implications for disease regulation. J. Neuroimmunol. 128:000.
  27. Adema, G. J., F. Hartgers, R. Verstraten, E. de Vries, G. Marland, S. Menon, J. Foster, Y. Xu, P. Nooyen, T. McClanahan, et al 1997. A dendritic-cell-derived C-C chemokine that preferentially attracts naive T cells. Nature 387:713.[Medline]
  28. Vissers, J. L., F. C. Hartgers, E. Lindhout, M. B. Teunissen, C. G. Figdor, G. J. Adema. 2001. Quantitative analysis of chemokine expression by dendritic cell subsets in vitro and in vivo. J. Leukocyte Biol. 69:785.[Abstract/Free Full Text]
  29. Zingoni, A., H. Soto, J. A. Hedrick, A. Stoppacciaro, C. T. Storlazzi, F. Sinigaglia, D. D’Ambrosio, A. O’Garra, D. Robinson, M. Rocchi, et al 1998. The chemokine receptor CCR8 is preferentially expressed in Th2 but not Th1 cells. J. Immunol. 161:547.[Abstract/Free Full Text]



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 J. Immunol.Home page
S. H. Kim, N. R. Bianco, W. J. Shufesky, A. E. Morelli, and P. D. Robbins
Effective Treatment of Inflammatory Disease Models with Exosomes Derived from Dendritic Cells Genetically Modified to Express IL-4
J. Immunol., August 15, 2007; 179(4): 2242 - 2249.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. R. Beaty, C. E. Rose Jr., and S.-s. J. Sung
Diverse and Potent Chemokine Production by Lung CD11bhigh Dendritic Cells in Homeostasis and in Allergic Lung Inflammation
J. Immunol., February 1, 2007; 178(3): 1882 - 1895.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
G. Penna, S. Amuchastegui, N. Giarratana, K. C. Daniel, M. Vulcano, S. Sozzani, and L. Adorini
1,25-Dihydroxyvitamin D3 Selectively Modulates Tolerogenic Properties in Myeloid but Not Plasmacytoid Dendritic Cells
J. Immunol., January 1, 2007; 178(1): 145 - 153.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
A. Hosmalin and P. Lebon
Type I interferon production in HIV-infected patients
J. Leukoc. Biol., November 1, 2006; 80(5): 984 - 993.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. L. Fanning, T. C. George, D. Feng, S. B. Feldman, N. J. Megjugorac, A. G. Izaguirre, and P. Fitzgerald-Bocarsly
Receptor Cross-Linking on Human Plasmacytoid Dendritic Cells Leads to the Regulation of IFN-{alpha} Production
J. Immunol., November 1, 2006; 177(9): 5829 - 5839.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
D. Ding, H. Mehta, W. J. McCune, and M. J. Kaplan
Aberrant Phenotype and Function of Myeloid Dendritic Cells in Systemic Lupus Erythematosus
J. Immunol., November 1, 2006; 177(9): 5878 - 5889.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. Osawa, S. Iho, R. Takauji, H. Takatsuka, S. Yamamoto, T. Takahashi, S. Horiguchi, Y. Urasaki, T. Matsuki, and S. Fujieda
Collaborative Action of NF-{kappa}B and p38 MAPK Is Involved in CpG DNA-Induced IFN-{alpha} and Chemokine Production in Human Plasmacytoid Dendritic Cells
J. Immunol., October 1, 2006; 177(7): 4841 - 4852.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
F. Groot, T. M. M. van Capel, M. L. Kapsenberg, B. Berkhout, and E. C. de Jong
Opposing roles of blood myeloid and plasmacytoid dendritic cells in HIV-1 infection of T cells: transmission facilitation versus replication inhibition
Blood, September 15, 2006; 108(6): 1957 - 1964.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
L. Chen, M. Arora, M. Yarlagadda, T. B. Oriss, N. Krishnamoorthy, A. Ray, and P. Ray
Distinct Responses of Lung and Spleen Dendritic Cells to the TLR9 Agonist CpG Oligodeoxynucleotide
J. Immunol., August 15, 2006; 177(4): 2373 - 2383.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
B. Piqueras, J. Connolly, H. Freitas, A. K. Palucka, and J. Banchereau
Upon viral exposure, myeloid and plasmacytoid dendritic cells produce 3 waves of distinct chemokines to recruit immune effectors
Blood, April 1, 2006; 107(7): 2613 - 2618.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Infantino, B. Moepps, and M. Thelen
Expression and Regulation of the Orphan Receptor RDC1 and Its Putative Ligand in Human Dendritic and B Cells
J. Immunol., February 15, 2006; 176(4): 2197 - 2207.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
C. Nicolo, G. Di Sante, M. Orsini, S. Rolla, S. Columba-Cabezas, V. R. Spica, G. Ricciardi, B. M. C. Chan, and F. Ria
Mycobacterium tuberculosis in the adjuvant modulates the balance of Th immune response to self-antigen of the CNS without influencing a "core" repertoire of specific T cells
Int. Immunol., February 1, 2006; 18(2): 363 - 374.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
M. Del Corno, M. C. Gauzzi, G. Penna, F. Belardelli, L. Adorini, and S. Gessani
Human Immunodeficiency Virus Type 1 gp120 and Other Activation Stimuli Are Highly Effective in Triggering Alpha Interferon and CC Chemokine Production in Circulating Plasmacytoid but Not Myeloid Dendritic Cells
J. Virol., October 1, 2005; 79(19): 12597 - 12601.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
N. Bendriss-Vermare, S. Burg, H. Kanzler, L. Chaperot, T. Duhen, O. de Bouteiller, M. D'agostini, J.-M. Bridon, I. Durand, J. M. Sederstrom, et al.
Virus overrides the propensity of human CD40L-activated plasmacytoid dendritic cells to produce Th2 mediators through synergistic induction of IFN-{gamma} and Th1 chemokine production
J. Leukoc. Biol., October 1, 2005; 78(4): 954 - 966.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
A. Fuchs, M. Cella, T. Kondo, and M. Colonna
Paradoxic inhibition of human natural interferon-producing cells by the activating receptor NKp44
Blood, September 15, 2005; 106(6): 2076 - 2082.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
M. Urosevic, R. Dummer, C. Conrad, M. Beyeler, E. Laine, G. Burg, and M. Gilliet
Disease-Independent Skin Recruitment and Activation of Plasmacytoid Predendritic Cells Following Imiquimod Treatment
J Natl Cancer Inst, August 3, 2005; 97(15): 1143 - 1153.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
E. Schutyser, A. Richmond, and J. Van Damme
Involvement of CC chemokine ligand 18 (CCL18) in normal and pathological processes
J. Leukoc. Biol., July 1, 2005; 78(1): 14 - 26.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
S. Tabata, N. Kadowaki, T. Kitawaki, T. Shimaoka, S. Yonehara, O. Yoshie, and T. Uchiyama
Distribution and kinetics of SR-PSOX/CXCL16 and CXCR6 expression on human dendritic cell subsets and CD4+ T cells
J. Leukoc. Biol., May 1, 2005; 77(5): 777 - 786.
[Abstract] [Full Text] [PDF]

Home page
 CVIHome page
E. Chung, S. B. Amrute, K. Abel, G. Gupta, Y. Wang, C. J. Miller, and P. Fitzgerald-Bocarsly
Characterization of Virus-Responsive Plasmacytoid Dendritic Cells in the Rhesus Macaque
Clin. Vaccine Immunol., March 1, 2005; 12(3): 426 - 435.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
A. Mazzoni and D. M. Segal
Controlling the Toll road to dendritic cell polarization
J. Leukoc. Biol., May 1, 2004; 75(5): 721 - 730.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
N. J. Megjugorac, H. A. Young, S. B. Amrute, S. L. Olshalsky, and P. Fitzgerald-Bocarsly
Virally stimulated plasmacytoid dendritic cells produce chemokines and induce migration of T and NK cells
J. Leukoc. Biol., March 1, 2004; 75(3): 504 - 514.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
A. Izaguirre, B. J. Barnes, S. Amrute, W.-S. Yeow, N. Megjugorac, J. Dai, D. Feng, E. Chung, P. M. Pitha, and P. Fitzgerald-Bocarsly
Comparative analysis of IRF and IFN-alpha expression in human plasmacytoid and monocyte-derived dendritic cells
J. Leukoc. Biol., December 1, 2003; 74(6): 1125 - 1138.
[Abstract] [Full Text]

Home page
 Infect. Immun.Home page
K. Muller, S. Bischof, F. Sommer, M. Lohoff, W. Solbach, and T. Laskay
Differential Production of Macrophage Inflammatory Protein 1{gamma} (MIP-1{gamma}), Lymphotactin, and MIP-2 by CD4+ Th Subsets Polarized In Vitro and In Vivo
Infect. Immun., November 1, 2003; 71(11): 6178 - 6183.
[Abstract] [Full Text] [PDF]

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