VISTA nonredundantly regulates proliferation and CD69low γδ T cell accumulation in the intestine in murine sepsis.

Autor:	Gray CC; Division of Surgical Research, Department of Surgery, Brown University, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, United States., Armstead BE; Division of Surgical Research, Department of Surgery, Brown University, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, United States.; Pathobiology Graduate Program, Brown University, Box G-B495, Providence, RI 02912, United States., Chung CS; Division of Surgical Research, Department of Surgery, Brown University, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, United States., Chen Y; Division of Surgical Research, Department of Surgery, Brown University, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, United States., Ayala A; Division of Surgical Research, Department of Surgery, Brown University, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, United States.; Pathobiology Graduate Program, Brown University, Box G-B495, Providence, RI 02912, United States.
Jazyk:	angličtina
Zdroj:	Journal of leukocyte biology [J Leukoc Biol] 2024 May 29; Vol. 115 (6), pp. 1005-1019.
DOI:	10.1093/jleuko/qiad149
Abstrakt:	Sepsis is a dysregulated systemic immune response to infection i.e. responsible for ∼35% of in-hospital deaths at a significant fiscal healthcare cost. Our laboratory, among others, has demonstrated the efficacy of targeting negative checkpoint regulators (NCRs) to improve survival in a murine model of sepsis, cecal ligation and puncture (CLP). B7-CD28 superfamily member, V-domain immunoglobulin suppressor of T cell activation (VISTA), is an ideal candidate for strategic targeting in sepsis. VISTA is a 35 to 45 kDa type 1 transmembrane protein with unique biology that sets it apart from all other NCRs. We recently reported that VISTA-/- mice had a significant survival deficit post-CLP, which was rescued upon adoptive transfer of a VISTA-expressing pMSCV-mouse Foxp3-EF1α-GFP-T2A-puro stable Jurkat cell line (Jurkatfoxp3 T cells). Based on our prior study, we investigated the effector cell target of Jurkatfoxp3 T cells in VISTA-/- mice. γδ T cells are a powerful lymphoid subpopulation that require regulatory fine-tuning by regulatory T cells to prevent overt inflammation/pathology. In this study, we hypothesized that Jurkatfoxp3 T cells nonredundantly modulate the γδ T cell population post-CLP. We found that VISTA-/- mice have an increased accumulation of intestinal CD69low γδ T cells, which are not protective in murine sepsis. Adoptive transfer of Jurkatfoxp3 T cells decreased the intestinal γδ T cell population, suppressed proliferation, skewed remaining γδ T cells toward a CD69high phenotype, and increased soluble CD40L in VISTA-/- mice post-CLP. These results support a potential regulatory mechanism by which VISTA skews intestinal γδ T cell lineage representation in murine sepsis. Competing Interests: Conflict of interest statement. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu