title: P-selectin glycoprotein ligand-1 modulates immune inflammatory responses in the enteric lamina propria.
abstract: P-selectin glycoprotein ligand-1 (PSGL-1), a leukocyte adhesion receptor that interacts with selectins, induces a tolerogenic programme in bone marrow-derived dendritic cells (DCs), which in turn promotes the generation of T regulatory (Treg) lymphocytes. In the present study, we have used a mouse model of dextran sulphate sodium (DSS)-induced colitis and studied the characteristics of the inflammatory cell infiltrate in the lamina propria (LP), mesenteric lymph nodes (mLNs) and Peyer's patches (PPs) to assess the possible role of PSGL-1 in the modulation of the enteric immune response. We have found that untreated PSGL-1-deficient mice showed an altered proportion of innate and adaptive immune cells in mLNs and PPs as well as an activated phenotype of macrophages and DCs in the colonic LP that mainly produced pro-inflammatory cytokines. Administration of an anti-PSGL-1 antibody also reduced the total numbers of macrophages, DCs and B cells in the colonic LP, and induced a lower expression of MHC-II by DCs and macrophages. After DSS treatment, PSGL-1(-/-) mice developed colitis earlier and with higher severity than wild-type (WT) mice. Accordingly, the colonic LP of these animals showed an enhanced number of Th1 and Th17 lymphocytes, with enhanced synthesis of IL-1α, IL-6 and IL-22, and increased activation of LP macrophages. Together, our data indicate that PSGL-1 has a relevant homeostatic role in the gut-associated lymphoid tissue under steady-state conditions, and that this adhesion receptor is able to down-regulate the inflammatory phenomenon in DSS-induced colitis.
authors: Departamento de Biología Vascular e Inflamación, CNIC, C/Melchor Fernández Almagro, 28034 Madrid, Spain.
authors: Norman
authors: N
authors: Nuñez-Andrade
authors: Amalia
authors: A
authors: Lamana
authors: David
authors: D
authors: Sancho
authors: Javier P
authors: JP
authors: Gisbert
authors: Roberto
authors: R
authors: Gonzalez-Amaro
authors: Francisco
authors: F
authors: Sanchez-Madrid
authors: Ana
authors: A
authors: Urzainqui
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D003106:Colon / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D016264:Dextran Sulfate; D006706:Homeostasis / Q000276:immunology; D018928:Immunity, Mucosal; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000276:immunology*; D008643:Mesentery; D051379:Mice; D008810:Mice, Inbred C57BL; D010581:Peyer's Patches / Q000276:immunology; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D016264:Dextran Sulfate