Macrophage-dependent neutrophil recruitment is impaired under conditions of increased intestinal permeability in JAM-A-deficient mice.

Junctional adhesion molecule-A (JAM-A) is a transmembrane glycoprotein expressed on leukocytes, endothelia, and epithelia that regulates biological processes including barrier function and immune responses. While JAM-A has been reported to facilitate tissue infiltration of leukocytes under inflammatory conditions, the contributions of leukocyte-expressed JAM-A in vivo remain unresolved. We investigated the role of leukocyte-expressed JAM-A in acute peritonitis induced by zymosan, lipopolysaccharide (LPS), or TNFα using mice with selective loss of JAM-A in myelomonocytic cells (LysM-Cre;Jam-a^fl/fl). Surprisingly, in LysM-Cre;Jam-a^fl/fl mice, loss of JAM-A did not affect neutrophil recruitment into the peritoneum in response to zymosan, LPS, or TNFα although it was significantly reduced in Jam-a^KO mice. In parallel, Jam-a^KO peritoneal macrophages exhibited diminished CXCL1 chemokine production and decreased activation of NF-kB, whereas those from LysM-Cre;Jam-a^fl/fl mice were unaffected. Using Villin-Cre;Jam-a^fl/fl mice, targeted loss of JAM-A on intestinal epithelial cells resulted in increased intestinal permeability along with reduced peritoneal migration as well as lower levels of CXCL1 and active NF-kB similar to that observed in Jam-a^KO animals. Interestingly, in germ-free Villin-Cre;Jam-a^fl/fl mice, duanyu1451 recruitment was unaffected suggesting dependence on gut microbiota. Such observations highlight the functional link between a leaky gut and regulation of innate immune responses.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}