title: CXCL10-producing mucosal CD4+ T cells, NK cells, and NKT cells are associated with chronic colitis in IL-10(-/-) mice, which can be abrogated by anti-CXCL10 antibody inhibition.
abstract: We have shown previously that there is a temporal increase in the levels of CXCL10 and CXCR3 mRNA during spontaneous murine colitis. We now show that CXCL10 is significantly expressed by mucosal CD4+ T cells, natural killer (NK) cells, and NKT cells, but not by dendritic cells (DCs), during chronic murine colitis. CXCL10 blockade alleviated chronic colitis and attenuated the associated increase in serum amyloid A (SAA), interleukin-12 (IL-12)p40, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-1 alpha, and IL-1 beta levels as well as in the number of CD4+ T, NKT, and NK cells that express CXCL10 and CXCR3, compared with groups treated with control antibody (Ab). After CXCL10 blockade, the number of CXCR3+ DCs in the mesenteric lymph nodes (MLNs) and Peyer's patches (PPs) were increased to levels found before the onset of colitis. In contrast, the numbers of splenic and intestinal lamina propria (LP) CXCR3+ DCs were reduced after anti-CXCL10 Ab treatment, compared with controls. Ex vivo antigen and CXCL10 stimulation of mucosal cells caused an increase in MHC class II, CD40, and CD86 as well as a decrease in CD30 ligand (CD30L) expression by DCs. This study provides insights into CXCL10 expression during inflammatory bowel disease (IBD) and the cellular and molecular mechanisms of CXCL10-mediated colitis. Our data also support the premise that CXCL10 blockade can attenuate chronic colitis by preventing the activation and recruitment of CXCR3+ leukocytes during IBD.
authors: Department of Microbiology and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors: Udai P
authors: UP
authors: Singh
authors: Shailesh
authors: S
authors: Singh
authors: Rajesh
authors: R
authors: Singh
authors: Yingzi
authors: Y
authors: Cong
authors: Dennis D
authors: DD
authors: Taub
authors: James W
authors: JW
authors: Lillard
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D054357:Chemokine CXCL10 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology; D003092:Colitis / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D018928:Immunity, Mucosal / Q000276:immunology*; D018836:Inflammation Mediators; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics; D053762:Interleukin-12 Subunit p40 / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000906:Antibodies; D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; C515188:Cxcr3 protein, mouse; D018836:Inflammation Mediators; D053762:Interleukin-12 Subunit p40; D054367:Receptors, CXCR3; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma