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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0901936v1 184/4/2026    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Niess, J. H. Articles by Adler, G. Search for Related Content PubMed PubMed Citation Articles by Niess, J. H. Articles by Adler, G.

Enteric Flora Expands Gut Lamina Propria CX₃CR1⁺ Dendritic Cells Supporting Inflammatory Immune Responses under Normal and Inflammatory Conditions

Department of Internal Medicine I, Ulm University, Ulm, Germany

CD103 or CX₃CR1 surface expression defines distinct dendritic cells (DCs) and macrophages in the murine lamina propria of the colon (cLP). We investigated the surface marker and functional phenotype of CD103⁺ and CX₃CR1⁺ cLP DCs and their role in transfer colitis. cLP CD11c⁺ cells were isolated from specific pathogen-free or germ-free mice to elucidate the role of the commensal flora in their development. The cLP CD11c⁺ cells are a heterogeneous cell population that includes 16% CX₃CR1⁺, 34% CD103⁺, 30% CD103^–CX₃CR1^– DCs, and 17% CD68^+/F4/80⁺CX₃CR1⁺CD11c⁺ macrophages. All DCs expressed high levels of MHC II but low levels of costimulatory (CD40, CD86, and CD80) and coinhibitory (programmed death ligand-1) molecules. Ex vivo confocal microscopy demonstrated that CX₃CR1⁺CD11c⁺ cells, but not CD103⁺ DCs, were reduced in the cLP of germ-free (CX₃CR1-GFP) mice. The absence of the enteric flora prevents the formation of transepithelial processes by the CX₃CR1⁺ DCs. CX₃CR1⁺ DCs preferentially supported Th1/Th17 CD4 T cell differentiation. CD103⁺ DCs preferentially induced the differentiation of Foxp3-expressing regulatory T cells. The stimulation of cLP DCs with fractalkine/CX₃CL1 increased the release of IL-6 and TNF-. In the absence of CX₃CR1, the CD45RB^high CD4 transfer colitis was suppressed and associated with reduced numbers of DCs in the mesenteric lymph nodes and a reduction in serum IFN- and IL-17. The local bacteria-driven accumulation of CX₃CR1⁺ DCs seems to support inflammatory immune responses.

Address correspondence and reprint requests to Dr. Jan-Hendrik Niess, Department of Internal Medicine I, University of Ulm, Albert-Einstein-Allee 23, D-89081 Ulm, Germany. E-mail address: jan-hendrik.niess{at}uniklinik-ulm.de

This work was supported by Grant Ni 575/4-1 from the Deutsche Forschungsgemeinschaft (to J.H.N.).

The online version of this article contains supplemental material.

Abbreviations used in this paper:

cLP, lamina propria of the colon; DC, dendritic cell; DN, double-negative; FCM, flow cytometry; GF, germ-free; LP, lamina propria; MLN, mesenteric lymph node; ODN, oligodeoxynucleotide; pDC, plasmacytoid dendritic cell; PD-L1, programmed death ligand-1; siLP, lamina propria of small intestine; SPF, specific pathogen-free; T_reg, regulatory T.