| First Author | Luissint AC | Year | 2019 |
| Journal | Mucosal Immunol | Volume | 12 |
| Issue | 3 | Pages | 668-678 |
| PubMed ID | 30745566 | Mgi Jnum | J:295763 |
| Mgi Id | MGI:6454360 | Doi | 10.1038/s41385-019-0143-7 |
| Citation | Luissint AC, et al. (2019) Macrophage-dependent neutrophil recruitment is impaired under conditions of increased intestinal permeability in JAM-A-deficient mice. Mucosal Immunol 12(3):668-678 |
| abstractText | 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 TNFalpha 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 (PMN) recruitment into the peritoneum in response to zymosan, LPS, or TNFalpha 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 PMN 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, PMN recruitment was unaffected suggesting dependence on gut microbiota. Such observations highlight the functional link between a leaky gut and regulation of innate immune responses. |
