Gut Helicobacter presentation by multiple dendritic cell subsets enables context-specific regulatory T cell generation

Generation of tolerogenic peripheral regulatory T (pTreg) cells is commonly thought to involve CD103 gut dendritic cells (DCs), yet their role in commensal-reactive pTreg development is unclear. Using two Helicobacter specific T cell receptor (TCR) transgenic mouse lines, we found that both CD103 an...

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Veröffentlicht in:eLife 2021-02, Vol.10
Hauptverfasser: Russler-Germain, Emilie V, Yi, Jaeu, Young, Shannon, Nutsch, Katherine, Wong, Harikesh S, Ai, Teresa L, Chai, Jiani N, Durai, Vivek, Kaplan, Daniel H, Germain, Ronald N, Murphy, Kenneth M, Hsieh, Chyi-Song
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Sprache:eng
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Zusammenfassung:Generation of tolerogenic peripheral regulatory T (pTreg) cells is commonly thought to involve CD103 gut dendritic cells (DCs), yet their role in commensal-reactive pTreg development is unclear. Using two Helicobacter specific T cell receptor (TCR) transgenic mouse lines, we found that both CD103 and CD103 migratory, but not resident, DCs from the colon-draining mesenteric lymph node presented Helicobacter antigens to T cells ex vivo. Loss of most CD103 migratory DCs in vivo using murine genetic models did not affect the frequency of Helicobacter-specific pTreg cell generation or induce compensatory tolerogenic changes in the remaining CD103 DCs. By contrast, activation in a Th1-promoting niche in vivo blocked Helicobacter-specific pTreg generation. Thus, these data suggest a model where DC-mediated effector T cell differentiation is 'dominant', necessitating that all DC subsets presenting antigen are permissive for pTreg cell induction to maintain gut tolerance.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.54792