Cutting Edge: Dual Function of PPAR? in CD11c+ Cells Ensures Immune Tolerance in the Airways.

ABSTRACT: The respiratory tract maintains immune homeostasis despite constant provocation by environmental Ags. Failure to induce tolerogenic responses to allergens incites allergic inflammation. Despite the understanding that APCs have a crucial role in maintaining immune tolerance, the underlying mechanisms are poorly understood. Using mice with a conditional deletion of peroxisome proliferator-activated receptor ? (PPAR?) in CD11c(+) cells, we show that PPAR? performs two critical functions in CD11c(+) cells to induce tolerance, thereby preserving immune homeostasis. First, PPAR? was crucial for the induction of retinaldehyde dehydrogenase (aldh1a2) selectively in CD103(+) dendritic cells, which we recently showed promotes Foxp3 expression in naive CD4(+) T cells. Second, in all CD11c(+) cells, PPAR? was required to suppress expression of the Th17-skewing cytokines IL-6 and IL-23p19. Also, lack of PPAR? in CD11c(+) cells induced p38 MAPK activity, which was recently linked to Th17 development. Thus, PPAR? favors immune tolerance by promoting regulatory T cell generation and blocking Th17 differentiation.

SUBMITTER: Khare A 

PROVIDER: S-EPMC4490989 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature