title: Local Inflammatory Cues Regulate Differentiation and Persistence of CD8+Tissue-Resident Memory T Cells.
abstract: Many pathogens initiate infection at mucosal surfaces, and tissue-resident memory T (Trm) cells play an important role in protective immunity, yet the tissue-specific signals that regulate Trm differentiation are poorly defined. During Yersinia infection, CD8+T cell recruitment to areas of inflammation within the intestine is required for differentiation of the CD103-CD69+Trm subset. Intestinal proinflammatory microenvironments have elevated interferon (IFN)-β and interleukin-12 (IL-12), which regulated Trm markers, including CD103. Type I interferon-receptor- or IL-12-receptor-deficient T cells functioned similarly to wild-type (WT) cells during infection; however, the inability of T cells to respond to inflammation resulted in defective differentiation of CD103-CD69+Trm cells and reduced Trm persistence. Intestinal macrophages were the main producers of IFN-β and IL-12 during infection, and deletion of CCR2+IL-12-producing cells reduced the size of the CD103-Trm population. These data indicate that intestinal inflammation drives phenotypic diversity and abundance of Trm cells for optimal tissue-specific immunity.
authors.affiliation: Department of Immunology, University of Washington, Seattle, WA 98109, USA. Electronic address: t.bergsbaken@rutgers.edu.
authors.forename: Tessa
authors.initials: T
authors.lastname: Bergsbaken
authors.affiliation: Department of Immunology, University of Washington, Seattle, WA 98109, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bevan
authors.affiliation: Department of Immunology, University of Washington, Seattle, WA 98109, USA. Electronic address: pfink@uw.edu.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Fink
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism; D000998:Antiviral Agents / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D007156:Immunologic Memory / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D039001:Integrin alpha Chains / Q000235:genetics / Q000378:metabolism; D007372:Interferons / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007422:Intestines / Q000276:immunology*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D054390:Receptors, CCR2 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015012:Yersinia pseudotuberculosis Infections / Q000276:immunology*; D000099192:CD69 Antigens
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000998:Antiviral Agents; D039001:Integrin alpha Chains; D007372:Interferons; D018664:Interleukin-12; D037181:Lectins, C-Type; D054390:Receptors, CCR2; D016212:Transforming Growth Factor beta; D000099192:CD69 Antigens; C515334:CCR2 protein, human; C091367:alpha E integrins
keywords: CD103; IL-12; bacterial infection; tissue-resident memory T cells