These studies will provide new insights into the region specific regulatory programs of DCs in mucosal surfaces. We have identified a mucosal plasmacytoid dendritic cell (pDC) subset that has a critical role in limiting intestinal inflammation thereby promoting tissue reconstruction and mucosal restitution. This pDC subset appears as a major DC subset in the intestine during colitis to direct mucosa-specific T cell functions essential for the resolution of inflammation. We hypothesize that mucosal pDCs are principal mediators of mucosal repair responses by controlling the intestine-specific regulatory phenotypes of Foxp3+ Tregs and Th17 cells. We will define key mechanisms that allow regulatory mucosal pDCs to effectively suppress inflammatory signals and to mediate mucosal protection. Defining the functional role of this newly discovered pDC subset in the regulation of mucosal inflammation will provide pivotal insights into the mechanisms that mediate mucosa specific control of regulatory T cells required for tissue repair in the highly antigenic environment of the intestine.
A more precise definition of the function of specialized dendritic cells in the regulation of mucosal T cells is required for our understanding of the mechanisms which control intestinal inflammation. We will define the functional role of a newly discovered mucosal dendritic cell subset in the regulation of mucosal inflammation to provide pivotal insights into the mechanisms that mediate mucosa-specific control of regulatory T cells required for tissue repair.
|Mohanan, Vishnu; Nakata, Toru; Desch, A Nicole et al. (2018) C1orf106 is a colitis risk gene that regulates stability of epithelial adherens junctions. Science 359:1161-1166|
|Kim, Young-In; Song, Joo-Hye; Ko, Hyun-Jeong et al. (2018) CX3CR1+ Macrophages and CD8+ T Cells Control Intestinal IgA Production. J Immunol 201:1287-1294|
|Maldonado-Contreras, Ana; Birtley, James R; Boll, Erik et al. (2017) Shigella depends on SepA to destabilize the intestinal epithelial integrity via cofilin activation. Gut Microbes 8:544-560|
|Ravindran, Ethiraj; Hu, Hao; Yuzwa, Scott A et al. (2017) Homozygous ARHGEF2 mutation causes intellectual disability and midbrain-hindbrain malformation. PLoS Genet 13:e1006746|
|Bouziat, Romain; Hinterleitner, Reinhard; Brown, Judy J et al. (2017) Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease. Science 356:44-50|
|Li, Yang; Basavappa, Megha; Lu, Jinfeng et al. (2016) Induction and suppression of antiviral RNA interference by influenza A virus in mammalian cells. Nat Microbiol 2:16250|
|O'Keeffe, Michael S; Song, Joo-Hye; Liao, Gongxian et al. (2015) SLAMF4 Is a Negative Regulator of Expansion of Cytotoxic Intraepithelial CD8+ T Cells That Maintains Homeostasis in the Small Intestine. Gastroenterology 148:991-1001.e4|
|Lammers, Karen M; Chieppa, Marcello; Liu, Lunhua et al. (2015) Gliadin Induces Neutrophil Migration via Engagement of the Formyl Peptide Receptor, FPR1. PLoS One 10:e0138338|
|Liao, Gongxian; O'Keeffe, Michael S; Wang, Guoxing et al. (2014) Glucocorticoid-Induced TNF Receptor Family-Related Protein Ligand is Requisite for Optimal Functioning of Regulatory CD4(+) T Cells. Front Immunol 5:35|
|Sundberg, Thomas B; Choi, Hwan Geun; Song, Joo-Hye et al. (2014) Small-molecule screening identifies inhibition of salt-inducible kinases as a therapeutic strategy to enhance immunoregulatory functions of dendritic cells. Proc Natl Acad Sci U S A 111:12468-73|
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