Browsing by Subject "dendritic cell"

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    The function of skin resident dendritic cells in CD4+ T cell differentiation
    (2016-08) Yao, Chen
    Skin-resident dendritic cells (DC) play a crucial role in initiation of adaptive immune responses against cutaneous pathogens as well as in the maintenance of peripheral tolerance. However, the immune response induced by skin DC against foreign antigen in the absence of adjuvants has not been addressed. Here we report that, using anti-huLangerin/ muLangerin antibodies, we could specifically target antigens to LC or CD103+ dermal DC. Targeting foreign peptide 2W1S by either LC or CD103+ dDC was sufficient for expansion of naïve CD4+ T cells and induction of T follicular helper cell (Tfh) differentiation. The expansion of Tfh specific to foreign peptide was accompanied by activation and expansion of antigen-specific B cells and the development of a robust antibody response that provided systemic protection against influenza infection. Using huLang LCΔMHC-II mice, we showed that CD4+ T cell proliferation was intact despite the MHC II deficiency on LC after targeting antigen to LC. We found that antigen targeted LC handed over antigen to CD11b+ dDC and DN dDC. We also showed MHC II deficient LC acquired MHC II in the lymph node through cross-dressing. This study reveals a major unappreciated function of skin DC in humoral response, and the communication between DC subsets, which provides insight into DC-targeted vaccine design.
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    In vivo functions of intestinal dendritic cells
    (2014-09) Welty, Nathan
    Dendritic cells (DCs) in the intestinal lamina propria (LP) are composed of two CD103+ subsets that differ in CD11b expression. We report here that langerin is expressed by human LP DCs and that transgenic human langerin drives expression in CD103+ CD11b+ LP DCs in mice. This subset was ablated in huLangerin-DTA mice, resulting in reduced LP Th17 cells without affecting Th1 or T reg cells. Notably, cognate DC-T cell interactions were not required for Th17 development, as this response was intact in huLangerin-Cre I-Ab flox mice. In contrast, responses to intestinal infection or flagellin administration were unaffected by the absence of CD103+ CD11b+ DCs. huLangerin-DTA x BatF3-/- mice lacked both CD103+ LP DC subsets, resulting in defective gut homing and fewer LP T reg cells. Despite these defects in LP DCs and resident T cells, we did not observe alterations of intestinal microbial communities. Thus, CD103+ LP DC subsets control T cell homeostasis through both non-redundant and overlapping mechanisms.