Migratory CD103+ dendritic cells suppress helminth-driven type 2 immunity through constitutive expression of IL-12

Bart Everts, Roxane Tussiwand, Leentje Dreesen, Keke C. Fairfax, Stanley Ching Cheng Huang, Amber M. Smith, Christina M. O'Neill, Wing Y. Lam, Brian T. Edelson, Joseph F. Urban, Kenneth M. Murphy, Edward J. Pearce

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

CD8α+ and CD103+ dendritic cells (DCs) play a central role in the development of type 1 immune responses. However, their role in type 2 immunity remains unclear. We examined this issue using Batf3-/- mice, in which both of these DC subsets are missing. We found that Th2 cell responses, and related events such as eosinophilia, alternative macrophage activation, and immunoglobulin class switching to IgG1, were enhanced in Batf3-/- mice responding to helminth parasites. This had beneficial or detrimental consequences depending on the context. For example, Batf3 deficiency converted a normally chronic intestinal infection with Heligmosomoides polygyrus into an infection that was rapidly controlled. However, liver fibrosis, an IL-13-mediated pathological consequence of wound healing in chronic schistosomiasis, was exacerbated in Batf3-/- mice infected with Schistosoma mansoni. Mechanistically, steady-state production of IL-12 by migratory CD103+ DCs, independent of signals from commensals or TLR-initiated events, was necessary and sufficient to exert the suppressive effects on Th2 response development. These findings identify a previously unrecognized role for migratory CD103+ DCs in antagonizing type 2 immune responses.

Original languageEnglish
Pages (from-to)35-51
Number of pages17
JournalJournal of Experimental Medicine
Volume213
Issue number1
DOIs
StatePublished - Jan 11 2016

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