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

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

来源：Journal of Experimental Medicine, 2016, 213(1): 35-51.

DOI：10.1084/jem.20150235

CD8 alpha(+) 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.

• 出版日期2016-1-11