| Title: |
Skin and heart allograft rejection solely by long-lived alloreactive TRM cells in skin of severe combined immunodeficient mice |
| Author: |
Tian, Qianchuan; Zhang, Zhaoqi; Tan, Liang; Yang, Fan; Xu, Yanan; Guo, Yinan; Wei, Dong; Wu, Changhong; Cao, Peng; Ji, Jiawei; Wang, Wei; Xie, Xubiao; Zhao, Yong |
| Abstract: |
Whether induced tissue-resident memory T (T-RM) cells in nonlymphoid organs alone can mediate allograft rejection is unknown. By grafting alloskin or heart into severe combined immunodeficient or Rag2KO mice in which a piece of induced CD4(+) and/or CD8(+)T(RM) cell-containing MHC-matched or syngeneic skin was transplanted in advance, we addressed this issue. The induced CD4(+)T(RM) cells in the skin alone acutely rejected alloskin or heart grafts. RNA-seq analysis showed that induced CD4(+) T-RM cells in skin favorably differentiated into T(H)17-like polarization during the secondary immune response. Inhibition of the key T(H)17 signaling molecule ROR gamma t attenuated T-RM cell-mediated graft rejection. Thus, we offer a unique mouse model to specifically study T-RM cell-mediated allograft rejection without the involvement of lymphocytes in lymphoid organs and tissues. Our study provides strong evidence supporting the hypothesis that long-lived alloreactive T-RM cells resident in other organs/tissues substantially contribute to organ allograft rejection. |
| Corresponding author: |
Zhao, Yong |
| Subject: |
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| Impact Factor: |
14.972 |
| Authors units: |
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| PubYear: |
2022 |
| Volume: |
8 |
| Issue: |
4 |
| Page: |
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| Journal: |
Science Advances |
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