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* Charité, Campus Mitte, Experimentelle Rheumatologie, c/o Deutsches Rheumaforschungszentrum, Berlin, Germany;
Charité, Campus Benjamin Franklin, Medizinische Klinik I, Berlin, Germany;
Charité, Campus Benjamin Franklin, Institut für Mikrobiologie und Hygiene, Berlin, Germany; and
Klaus Erb, Zentrum für Infektionsforschung, Universität Würzburg, Würzburg, Germany
T effector cells require selectin ligands to migrate into inflamed regions. In vitro, IL-12 promotes induction of these ligands as well as differentiation of CD4+ T cells into IFN-
-producing Th1 but not Th2 cells. STAT4 is strongly involved in these processes. However, the presence of selectin ligands on various T effector cell subsets in vivo points to more complex regulatory pathways. To clarify the role of the IL-12/STAT4 signaling pathway, we analyzed the impact of STAT4 deficiency on the expression of P-selectin ligands (P-lig) on CD4+ T cells in vitro and in vivo, including conditions of infection. In vitro, we found significant expression of P-lig upon activation not only in the presence, but also in the absence, of IL-12, which was independent of STAT4. TGF-
, an alternative inducer of selectin ligands in human T cells, was not effective in murine CD4+ T cells, suggesting a role of additional signaling pathways. In vivo, a significant impact of STAT4 for the generation of P-lig+CD4+ T cells was observed for cells from peripheral lymph nodes, but not for those from spleen or lung. However, upon infection with the Th2-inducing parasite Nippostrongylus brasiliensis, P-lig expression became dependent on STAT4 signaling. Interestingly, also the frequency of IL-4-producing cells was greatly diminished in absence of STAT4. These data reveal a hitherto unknown contribution of STAT4 to the generation of Th2 cells in parasite infection and suggest that signals inducing inflammation-seeking properties in vivo vary depending on environmental conditions, such as type of organ and infection.
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1 This work was supported by Deutsche Forschungsgemeinschaft Grants SFB 366 and SY 31/2-1.
2 Address correspondence and reprint requests to Dr. Uta Syrbe, Experimental Rheumatology, c/o Deutsches Rheumaforschungszentrum, Schumannstrasse 21/22, 10117 Berlin, Germany. E-mail address: syrbe{at}drfz.de
3 Current address: Boehringer Ingelheim Pharma, 88397 Biberach an der Riss, Germany.
4 Abbreviations used in this paper: PSGL-1, P-selectin glycoprotein ligand 1; P-lig, P-selectin ligand; FucT, fucosyltransferase; C2GlcNAT, core 2 1,6-glucosaminyltransferase; MFI, mean fluorescence intensity.
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