TY - JOUR
T1 - Cutting edge
T2 - Role of osteopontin and integrin αv in T cell-mediated anti-inflammatory responses in endotoxemia
AU - Inoue, Makoto
AU - Shinohara, Mari L.
N1 - Publisher Copyright:
Copyright © 2015 by The American Association of Immunologists, Inc.
PY - 2015/6/15
Y1 - 2015/6/15
N2 - The immune system is equipped with mechanisms that downregulate hyperinflammation to avoid collateral damage. We demonstrated recently that unprimed T cells downregulate macrophage TNF production through direct interaction with macrophages in the spleen during LPS endotoxemia. How T cell migration toward macrophages occurs upon LPS injection is still not clear. In this study, we demonstrate that secreted osteopontin (sOPN) plays a role in the T cell migration to initiate the suppression of hyperinflammation during endotoxemia. Osteopontin levels in splenic macrophages were upregulated 2 h after LPS treatment, whereas T cell migration toward macrophages was observed 3 h after treatment. Neutralization of sOPN and blockade of its receptor, integrin αv, significantly inhibited CD4+ T cell migration and increased susceptibility to endotoxemia. Our study demonstrates that the sOPN/ integrin αv axis, which induces T cell chemotaxis toward macrophages, is critical for suppressing hyperinflammation during the first 3 h of endotoxemia.
AB - The immune system is equipped with mechanisms that downregulate hyperinflammation to avoid collateral damage. We demonstrated recently that unprimed T cells downregulate macrophage TNF production through direct interaction with macrophages in the spleen during LPS endotoxemia. How T cell migration toward macrophages occurs upon LPS injection is still not clear. In this study, we demonstrate that secreted osteopontin (sOPN) plays a role in the T cell migration to initiate the suppression of hyperinflammation during endotoxemia. Osteopontin levels in splenic macrophages were upregulated 2 h after LPS treatment, whereas T cell migration toward macrophages was observed 3 h after treatment. Neutralization of sOPN and blockade of its receptor, integrin αv, significantly inhibited CD4+ T cell migration and increased susceptibility to endotoxemia. Our study demonstrates that the sOPN/ integrin αv axis, which induces T cell chemotaxis toward macrophages, is critical for suppressing hyperinflammation during the first 3 h of endotoxemia.
UR - http://www.scopus.com/inward/record.url?scp=84931340406&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84931340406&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1500623
DO - 10.4049/jimmunol.1500623
M3 - Article
C2 - 25972484
AN - SCOPUS:84931340406
SN - 0022-1767
VL - 194
SP - 5595
EP - 5598
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -