Caspase-1 inhibition ameliorates murine acute graft versus host disease by modulating the Th1/Th17/Treg balance
In: International immunopharmacology, Jg. 94 (2020-11-09)
Online
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Zugriff:
Our previous studies have implicated Caspase-1 signaling in driving the proinflammatory state of acute graft versus host disease (aGVHD). Therefore, we aimed to elucidate the mechanism of Caspase-1 in in murine models of aGVHD through specific inhibition of its activity with the decoy peptide Ac-YVAD-CMK. We transplanted bone marrow from donor C57BL/6 (H-2b) mice into recipient BALB/c (H-2Kd) mice and randomized the recipients into the following treatment cohorts: (1) allogeneic hematopoietic stem cell transplantation and splenic cell infusion control (PBS group); (2) low dose Ac-YVAD-CMK (AC low group); (3) and high dose Ac-YVAD-CMK (AC high group). Indeed, we observed that Caspase-1 inhibition by Ac-YVAD-CMK ameliorated pathological damage and inflammation in the liver, lungs, and colon elicited by aGVHD. This was associated with reduced mortality secondary to aGVHD. Mechanistically, we found that Caspase-1 inhibition modulated donor T cell expansion, restored the balance of Th1/Th17/Treg subsets, and markedly decreased serum levels and aGVHD target organ mRNA expression of IL-1β, IL-18, and HMGB1. Thus, we demonstrate that inhibition of Caspase-1 by Ac-YVAD-CMK mitigates murine aGVHD by regulating Th1/Th17/Treg balance and attenuating its characteristic proinflammatory state.
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Caspase-1 inhibition ameliorates murine acute graft versus host disease by modulating the Th1/Th17/Treg balance
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Autor/in / Beteiligte Person: | Cheng, Hai ; Chen, Wei ; Kong, QingLing ; Su, Gui-Zhen ; Pan, Bin ; Zeng, Lingyu ; Xu, Kailin ; Zhu, Shengyun ; Cao, Jiang ; Qi, Kunming ; Wu, Qing-Yun ; Guo, Wentong ; Zhu, Feng ; Xu, Yan ; Li, Zhenyu ; Bhansali, Rahul ; Li, Miao |
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Zeitschrift: | International immunopharmacology, Jg. 94 (2020-11-09) |
Veröffentlichung: | 2020 |
Medientyp: | unknown |
ISSN: | 1878-1705 (print) |
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