Inflammatory Th1 and Th17 in the Intestine Are Each Driven by Functionally Specialized Dendritic Cells with Distinct Requirements for MyD88

• Autor(a) principal: Liang, Jie
• Data de Publicação: 2016
• Outros Autores: Huang, Hsin-I, Benzatti, Fernanda P. [UNESP], Karlsson, Amelia B., Zhang, Junyi J., Youssef, Nourhan, Ma, Averil, Hale, Laura P., Hammer, Gianna E.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1016/j.celrep.2016.09.091; http://hdl.handle.net/11449/162109

Normal dynamics between microbiota and dendritic cells (DCs) support modest numbers of T cells, yet these do not cause inflammation. The DCs that induce inflammatory T cells and the signals that drive this process remain unclear. Here, we demonstrate that small intestine DCs lacking the signaling attenuator A20 induce inflammatory T cells and that the signals perceived and antigen-presenting cell (APC) functions are unique for different DC subsets. Thus, although CD103(+)CD11b(+) DCs exclusively instruct IFN gamma(+) T cells, CD103(+)CD11b(+) DCs exclusively instruct IL-17(+) T cells. Surprisingly, APC functions of both DC subsets are upregulated in a MyD88-independent fashion. In contrast, CD103(-)CD11b(+) DCs instruct both IFN gamma(+) and IL-17(+) T cells, and only the IL-17-inducing APC functions require MyD88. In disease pathogenesis, both CD103(-)CD11b(+) and CD103(+)CD11b(+) DCs expand pathologic Th17 cells. Thus, in disease pathogenesis, specific DCs instruct specific inflammatory T cells.