TY - JOUR
T1 - Inhibition of Sphingosine-1-phosphate receptors in ischemia reperfusion injured autoimmunity-prone mice
AU - Edison, Jess
AU - Frattalone, Sharon
AU - Tracy, Christopher
AU - Woodard, Geoffrey E.
AU - Butts, Melissa
AU - Moratz, C. M.
N1 - Funding Information:
This work was supported by the U.S. Army Medical Research and Materiel Command , Department of Defense grant W81XWH-07-1-0286 and USUHS Intermural Grant C1833A .
Funding Information:
This work was supported by the Medical Research and Materiel Command grant W81XWH-07-1-0286 and USUHS Intermural Grant R0833A.
Publisher Copyright:
© 2016
PY - 2017/1/1
Y1 - 2017/1/1
N2 - B6.MRL/lpr mice, an autoimmune strain, have an accelerated injury time course, increased intensity of tissue damage, and increased CD4+ T cell infiltration in the mesenteric ischemia/reperfusion injury model. In this study, the mechanism by which CD4+ T cells were recruited into injured tissue was addressed. Fingolimod (FTY720) was utilized to assess the role of infiltrating CD4+ T cells. FTY720 treatment was more effective in attenuating injury in B6.MRL/lpr mice then in control mice. Reduced CD4+ cell infiltration and tissue injury correlated with decreased neutrophil infiltration and pro-inflammatory cytokine generation. Inhibiting downstream Sphingosine-1-phosphate (S1P) receptor signaling, specifically GαI mediated signaling, did not inhibit injury, suggesting differential utilization of the S1P receptors between control and MRL/lpr strains. Analysis of S1P receptor expression exposed a predominance of S1P2 in the B6.MRL/lpr strain. Reliance on alternate S1P receptors in the autoimmune strain will alter the progress of inflammation and tissue injury.
AB - B6.MRL/lpr mice, an autoimmune strain, have an accelerated injury time course, increased intensity of tissue damage, and increased CD4+ T cell infiltration in the mesenteric ischemia/reperfusion injury model. In this study, the mechanism by which CD4+ T cells were recruited into injured tissue was addressed. Fingolimod (FTY720) was utilized to assess the role of infiltrating CD4+ T cells. FTY720 treatment was more effective in attenuating injury in B6.MRL/lpr mice then in control mice. Reduced CD4+ cell infiltration and tissue injury correlated with decreased neutrophil infiltration and pro-inflammatory cytokine generation. Inhibiting downstream Sphingosine-1-phosphate (S1P) receptor signaling, specifically GαI mediated signaling, did not inhibit injury, suggesting differential utilization of the S1P receptors between control and MRL/lpr strains. Analysis of S1P receptor expression exposed a predominance of S1P2 in the B6.MRL/lpr strain. Reliance on alternate S1P receptors in the autoimmune strain will alter the progress of inflammation and tissue injury.
KW - Autoimmunity
KW - Inflammation: tissue injury T cells
KW - Sphingosine-1-phosphate
UR - http://www.scopus.com/inward/record.url?scp=85005870093&partnerID=8YFLogxK
U2 - 10.1016/j.cellimm.2016.10.005
DO - 10.1016/j.cellimm.2016.10.005
M3 - Article
C2 - 27816167
AN - SCOPUS:85005870093
SN - 0008-8749
VL - 311
SP - 63
EP - 70
JO - Cellular Immunology
JF - Cellular Immunology
ER -