Inflammatory Th1 and Th17 in the Intestine Are Each Driven by Functionally Specialized Dendritic Cells with Distinct Requirements for MyD88.
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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 IFNγ(+) 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 IFNγ(+) 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.
Published Version (Please cite this version)10.1016/j.celrep.2016.09.091
Publication InfoLiang, J; Huang, HI; Benzatti, FP; Karlsson, AB; Zhang, JJ; Youssef, Nourhan; ... Hammer, Gianna (2016). Inflammatory Th1 and Th17 in the Intestine Are Each Driven by Functionally Specialized Dendritic Cells with Distinct Requirements for MyD88. Cell Rep, 17(5). pp. 1330-1343. 10.1016/j.celrep.2016.09.091. Retrieved from https://hdl.handle.net/10161/13002.
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Professor of Pathology
The Hale laboratory employs techniques of cellular and molecular biology to study mechanisms responsible for the generation of both normal immune responses and immune-mediated diseases. Research in the laboratory is mainly focused on inflammatory bowel disease (IBD), an immune-mediated disorder that is hypothesized to result from the abnormal immune response of a genetically susceptible host to the antigens derived from enteric bacteria. Development of optimal treatments for disease require
Assistant Professor of Immunology
The study of microbial communities that reside on and within the human body (the microbiome) is considered one of the hottest areas of science today. It is now well appreciated that the microbiome has remarkable influence on diverse aspects of human health and disease. To understand how the microbiome exerts such influence, our lab seeks to define the mechanisms by which cells of the immune system interact with microbes that reside in the intestine. To the immune system, co-existence with mic
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