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P‐selectin glycoprotein ligand‐1 modulates immune inflammatory responses in the enteric lamina propria
Author(s) -
NuñezAndrade Norman,
Lamana Amalia,
Sancho David,
Gisbert Javier P,
GonzalezAmaro Roberto,
SanchezMadrid Francisco,
Urzainqui Ana
Publication year - 2011
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2850
Subject(s) - immune system , lamina propria , immunology , mesenteric lymph nodes , inflammation , selectin , dendritic cell , biology , chemistry , microbiology and biotechnology , epithelium , genetics
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. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.