IL-17 producing CD4+ T cells mediate accelerated ischemia/reperfusion-induced injury in autoimmunity-prone mice.
Elements of the innate and adaptive immune response have been implicated in the development of tissue damage after ischemic reperfusion (I/R). Here we demonstrate that T cells infiltrate the intestine of C57BL/6 mice subjected to intestinal I/R during the first hour of reperfusion. The intensity of the T cell infiltration was higher in B6.MRL/lpr mice subjected to intestinal I/R and reflected more severe tissue damage than that observed in control mice. Depletion of T cells limited I/R damage in B6.MRL/lpr mice, whereas repletion of B6.MRL/lpr lymph node-derived T cells into the I/R-resistant Rag-1(-/-) mouse reconstituted tissue injury. The tissue-infiltrating T cells were found to produce IL-17. Finally, IL-23 deficient mice, which are known not to produce IL-17, displayed significantly less intestinal damage when subjected to I/R. Our data assign T cells a major role in intestinal I/R damage by virtue of producing the pro-inflammatory cytokine IL-17.
Edgerton
Colin
C
Department of Medicine, Uniformed Services University for the Health Sciences, Bethesda, MD 20814, USA.
Crispín
José C
JC
Moratz
Chantal M
CM
Bettelli
Estelle
E
Oukka
Mohamed
M
Simovic
Milomir
M
Zacharia
Athina
A
Egan
Ryan
R
Chen
Jie
J
Dalle Lucca
Jurandir J
JJ
Juang
Yuang-Taung
YT
Tsokos
George C
GC
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000503:physiopathology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D020381:Interleukin-17 / Q000276:immunology*; D007422:Intestines / Q000276:immunology / Q000293:injuries / Q000503:physiopathology; D007511:Ischemia / Q000276:immunology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D015427:Reperfusion Injury / Q000276:immunology / Q000503:physiopathology*
D020381:Interleukin-17