Circulating memory-phenotype CD4⁺ T cells rapidly accumulate in the ischemic gut to exacerbate tissue injury in an innate manner.

Authors

Kosuke Sato, Shunichi Tayama, Akihisa Kawajiri, Jing Li, Ziying Yang, Ryoji Mitsuwaka, Feng Gao, Natsuki Asami, Reoka Aoki, Hiroyuki Nagashima, Kenshiro Matsuda, Chigusa Nakahashi-Oda, Yoichiro Iwakura, Akira Shibuya, Motoshi Wada, Naoto Ishii, Takeshi Kawabe

Published in

Cell reports. Volume 45. Issue 8. Pages 117745. Jul 29, 2026. Epub Jul 29, 2026.

Abstract

Memory-phenotype (MP) CD4⁺ T lymphocytes develop from peripheral naive precursors via self-recognition at homeostasis. While MP cells exert innate immune function in infectious and autoimmune contexts, their functional significance in ischemia-reperfusion injury (IRI) remains unclear. Here we show that blood-circulating MP lymphocytes rapidly infiltrate the gut in the absence of antigen recognition during intestinal IRI. This MP migration is directed by α₄β₇ that binds to vascular MAdCAM-1, with the latter's expression immediately upregulated by IRI-induced TNF-α. Once accumulated in the gut, MP cells respond to IL-12 to produce IFN-γ that elevates CXCL1 and CXCL2 levels and orchestrates neutrophils, thereby exaggerating tissue injury. Furthermore, such innate MP responses are operative in hepatic but not renal IRI. Together, our results reveal blood-circulating MP cells as a unique innate amplifier of IRI that rapidly accumulates in the gut to exacerbate tissue injury via neutrophil orchestration.

PMID:
42531132
Bibliographic data and abstract were imported from PubMed on 31 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.