4.7 Article

Intestinal lamina propria dendritic cells maintain T cell homeostasis but do not affect commensalism

Journal

JOURNAL OF EXPERIMENTAL MEDICINE
Volume 210, Issue 10, Pages 2011-2024

Publisher

ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20130728

Keywords

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Funding

  1. National Institutes of Health (NIH) [AR056632, AR060744]
  2. Dermatology Foundation
  3. American Skin Association
  4. Dr. Al Zelickson Family
  5. Warren and Henrietta Warwick fellowship
  6. University of Minnesota NIH MSTP [T32 GM008244]
  7. NIH [DK097856]

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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-A beta(fl/fl) 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.

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