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Role of CCR6 in the dysregulated systemic immune response during severe experimental sepsis
Author(s) -
Wen Haitao,
Hogaboam Cory M,
Kunkel Steven L
Publication year - 2006
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.20.4.a203-c
Subject(s) - c c chemokine receptor type 6 , sepsis , chemokine , lipopolysaccharide , cytokine , peritonitis , immune system , peritoneal cavity , immunology , medicine , tumor necrosis factor alpha , receptor , chemokine receptor , surgery
The innate immune role of the chemokine receptor CCR6 is not fully understood outside of its involvement in the chemotaxis of immature dendritic cells. In a severe experimental peritonitis sepsis model (murine cecal ligation and puncture‐CLP), CCR6‐deficient (CCR6 −/− ) mice were significantly protected from lethality compared with wild type (WT) controls. At 24 hours following CLP surgery, CCR6 −/− mice exhibited significantly lower bacterial and inflammatory cytokines/chemokines levels in the peritoneal cavity and blood. Flow cytometry analysis showed naïve CCR6 −/− mice had significantly lower number of F4/80 + cells in peritoneal cavities compared with naïve WT controls. Isolated naïve CCR6 −/− peritoneal macrophages (Mϕs) exhibited significantly less inflammatory cytokine synthesis at 24 hours after lipopolysaccharide stimulation compared with similarly treated WT Mϕs. Interestingly, peritoneal Mϕs isolated from CCR6 −/− mice at day 3 after CLP surgery exhibited significantly enhanced production of inflammatory cytokines in response to various Toll‐like receptor agonists compared with similarly treated WT Mϕs. Together, these data show that the presence of CCR6 contributes to the severity of septic responses through a mechanism that involves Mϕ activation. Supported by NIH grant HL31237