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

Emilie V. Russler-Germain, Jaeu Yi, Shannon Young, Katherine Nutsch, Harikesh S. Wong, Teresa L. Ai, Jiani N. Chai, Vivek Durai, Daniel H. Kaplan, Ronald N. Germain, Kenneth M. Murphy, Chyi Song Hsieh

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere54792
Pages (from-to)1-29
Number of pages29
JournaleLife
Volume10
DOIs
StatePublished - Feb 2021

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