title: CD45 regulates GM-CSF, retinoic acid and T-cell homing in intestinal inflammation.
abstract: CD45 is a leukocyte-specific tyrosine phosphatase important for T-cell development, and as a result, CD45-/-mice have substantially reduced numbers of T cells. Here we show that, upon dextran sodium sulfate (DSS)-induced colitis, CD45-/-mice have equivalent intestinal pathology and T-cell numbers in their colon as C57BL/6 mice and show enhanced weight loss. CD45-/-mice have a greater percentage of α4β7+T cells prior to and after colitis and an increased percentage of T cells producing inflammatory cytokines in the inflamed colon, suggesting that CD45-/-effector T cells preferentially home to the intestine. In DSS-induced colitis in CD45RAG-/-mice lacking an adaptive immune system, CD45 was required for optimal granulocyte-macrophage colony-stimulating factor (GM-CSF) and retinoic acid (RA) production by innate immune cells. Addition of CD45+/+T cells led to greater weight loss in the RAG-/-mice compared with CD45RAG-/-mice that correlated with reduced α4β7+T cells and lower recruitment to the colon of CD45RAG-/-mice in DSS-induced colitis. Addition of exogenous GM-CSF to CD45RAG-/-mice rescued RA production, increased colonic T-cell numbers, and increased weight loss. This demonstrates opposing effects of CD45 in innate and adaptive immune cells in proinflammatory responses and the expression of the gut-homing molecule, α4β7.
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Samarakoon
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Y A
authors.initials: YA
authors.lastname: Shim
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Dosanjh
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Crickmer
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Labonté-Raymond
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: A A
authors.initials: AA
authors.lastname: Arif
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Johnson
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000276:immunology / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D000950:Antigens, Ly; D016207:Cytokines; D018836:Inflammation Mediators; C527211:Klrb1c protein, mouse; D055651:NK Cell Lectin-Like Receptor Subfamily B; D014212:Tretinoin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016264:Dextran Sulfate; D017493:Leukocyte Common Antigens