Inflammatory Th1 and Th17 in the Intestine Are Each Driven by Functionally Specialized Dendritic Cells with Distinct Requirements for MyD88.
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2016-10-25
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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.
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Liang, Jie, Hsin-I Huang, Fernanda P Benzatti, Amelia B Karlsson, Junyi J Zhang, Nourhan Youssef, Averil Ma, Laura P Hale, et al. (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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Laura Pope Hale
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 requires a detailed understanding of mechanisms of disease pathogenesis. Thus current work in the laboratory is aimed at understanding triggers of intestinal inflammation and mechanisms of inflammation-associated neoplasia, in addition to developing novel therapies for IBD treatment. Ongoing research also includes investigating mechanisms that determine the immunogenicity of oral antigens, to develop novel adjuvants for oral vaccines. This work has relevance for pathogenesis and treatment of infectious diseases affecting the gastrointestinal tract, as well as for inflammatory bowel disease.
Dr. Hale is an expert in pathologic evaluation of colitis and immunodeficiency in both humans and mice and is board-certified in Anatomic and Clinical Pathology.
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