Single-cell immune profiling reveals a developmentally distinct CD4+ GM-CSF+ T-cell lineage that induces GI tract GVHD.

Autor:	Piper C; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI., Hainstock E; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI., Yin-Yuan C; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI., Chen Y; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI.; Blood Research Institute, Versiti, Milwaukee, WI; and., Khatun A; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI.; Blood Research Institute, Versiti, Milwaukee, WI; and., Kasmani MY; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI.; Blood Research Institute, Versiti, Milwaukee, WI; and., Evans J; Department of Pathology, and., Miller JA; Department of Pathology, and., Gorski J; Blood Research Institute, Versiti, Milwaukee, WI; and., Cui W; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI.; Blood Research Institute, Versiti, Milwaukee, WI; and., Drobyski WR; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI.; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2022 May 10; Vol. 6 (9), pp. 2791-2804.
DOI:	10.1182/bloodadvances.2021006084
Abstrakt:	Gastrointestinal (GI) tract involvement is a major determinant for subsequent morbidity and mortality arising during graft-versus-host disease (GVHD). CD4+ T cells that produce granulocyte-macrophage colony stimulating factor (GM-CSF) have emerged as central mediators of inflammation in this tissue site as GM-CSF serves as a critical cytokine link between the adaptive and innate arms of the immune system. However, cellular heterogeneity within the CD4+ GM-CSF+ T-cell population due to the concurrent production of other inflammatory cytokines has raised questions as to whether these cells have a common ontology or if a unique CD4+ GM-CSF+ subset exists that differs from other defined T helper subtypes. Using single-cell RNA sequencing analysis (scRNAseq), we identified two CD4+ GM-CSF+ T-cell populations that arose during GVHD and were distinguishable according to the presence or absence of interferon-γ (IFN-γ) coexpression. CD4+ GM-CSF+ IFN-γ- T cells, which emerged preferentially in the colon, had a distinct transcriptional profile, used unique gene regulatory networks, and possessed a nonoverlapping T-cell receptor repertoire compared with CD4+ GM-CSF+ IFN-γ+ T cells as well as all other transcriptionally defined CD4+ T-cell populations in the colon. Functionally, this CD4+ GM-CSF+ T-cell population contributed to pathologic damage in the GI tract that was critically dependent on signaling through the interleukin-17 (IL-7) receptor but was independent of type 1 interferon signaling. Thus, these studies help to unravel heterogeneity within CD4+ GM-CSF+ T cells that arise during GVHD and define a developmentally distinct colitogenic T helper subtype GM-CSF+ subset that mediates immunopathology. (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu