P2Y12 antagonism results in altered interactions between platelets and regulatory T cells during sepsis
P2Y12 antagonism results in altered interactions between platelets and regulatory T cells during sepsis
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DOI：
10.1002/jlb.3a0220-097r
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发表时间：
2020-11-26
影响因子：
5.5
通讯作者：
Liverani, Elisabetta
中科院分区：
文献类型：
--
作者：
Albayati, Samara;Vemulapalli, Harika;Liverani, Elisabetta
Sepsis is a complex clinical condition resulting from a serious bloodstream infection. With mortality rates as high as 50%, improved treatments are needed. Regulatory T cells (Tregs), a subset of T lymphocytes, promote the resolution of inflammation. Septic patients have elevated levels of circulating Tregs. Platelets influence the proliferation and activation of Tregs in vitro. However, modulating platelet-Tregs interaction during sepsis may restraing Treg proliferation, leading to the restoration of immunologic homeostasis. P2Y(12) is a purinergic receptor present on platelets and T lymphocytes. Blocking P2Y(12) improves the outcome of sepsis. We investigated whether blocking P2Y(12) alters platelet-Treg interaction in vivo. We used the murine model of sepsis, cecal ligation, and puncture (CLP) and we blocked P2Y(12) using the P2Y(12) antagonist, clopidogrel. Twenty-four hours after surgery, we measured Treg population sizes in the spleens of the Sham, CLP, and CLP + clopidogrel groups. We investigated the effect of blocking P2Y(12) in vitro using cocultures of human platelets and T cells with or without anti-CD3/CD28. P2Y(12) was blocked using AR-C69931MX. Treg population sizes were reduced in the septic mice treated with clopidogrel compared with untreated septic mice. Aggregation of platelets and CD4(+) T cells was reduced in treated CLP mice compared with untreated CLP mice. P2Y(12) antagonism changes how platelets influence T cells in vitro, depending on T-cell activation. In conclusion, blockade of the P2Y(12) signaling pathway restrains Treg proliferation in vivo and in vitro. Targeting platelets to control Treg proliferation and activity may be a promising strategy for treating sepsis.
