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Endogenous IL‐10 prevents LPS‐induced IFNgamma production in the human colonic mucosa
Author(s) -
Jarry Anne,
Bossard Celine,
Masson Damien,
Denis Marc G,
Laboisse Christian L
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a589-c
Subject(s) - intestinal mucosa , secretion , immune system , endogeny , immunology , tumor necrosis factor alpha , stimulation , biology , interleukin 8 , enterocolitis , cytokine , medicine , endocrinology
Interleukin 10 (IL‐10) is a key regulator of intestinal mucosal homeostasis in rodents, since IL‐10−/− mice spontaneously develop an enterocolitis. In humans, the role of endogeneous IL‐10 in the intestinal mucosa is unknown yet. To address this issue, we developed an explant culture system of human normal colonic mucosa microdissected from surgical resections, in which an IL‐10 depletion was performed using neutralizing anti‐IL‐10 antibodies. We showed that IL‐10 was constitutively expressed and secreted by the human normal colonic mucosa, the major source being epithelial cells. IL‐10‐depletion in 48h mucosa explant cultures elicited an inflammatory response consisting in high levels of IFNγ and much lower levels of TNFα (protein, mRNA levels). This Th1 immune response was triggered by bacterial LPS, as demonstrated by the abolition of IFNγ secretion after treatment with the LPS scavenger polymyxin B. Altogether, these findings are the first demonstration in the human colonic mucosa that IL‐10 ablation leads to a Th1‐mediated inflammatory response elicited by resident colitogenic cells via bacterial stimulation. These data are thus in favor of a pivotal role of endogeneous IL‐10 in the induction of mucosal anergy towards commensal bacteria stimulation. This work was supported in part by a grant (ACIM A03038 GS) from the French Ministère Délégué à la Recherche et aux Nouvelles Technologies.