95754 20230706131408.0 doi 10.1172/jci.insight.124465 sideral 120192 ART-2020-120192 eng Park, S. Granzyme A-producing T helper cells are critical for acute graft-versus-host disease 2020 Access copy available to the general public Unrestricted Acute graft-versus-host disease (aGVHD) can occur after hematopoietic cell transplant in patients undergoing treatment for hematological malignancies or inborn errors. Although CD4+ T helper (Th) cells play a major role in aGVHD, the mechanisms by which they contribute, particularly within the intestines, have remained elusive. We have identified a potentially novel subset of Th cells that accumulated in the intestines and produced the serine protease granzyme A (GrA). GrA+ Th cells were distinct from other Th lineages and exhibited a noncytolytic phenotype. In vitro, GrA+ Th cells differentiated in the presence of IL-4, IL-6, and IL-21 and were transcriptionally unique from cells cultured with either IL-4 or the IL-6/IL-21 combination alone. In vivo, both STAT3 and STAT6 were required for GrA+ Th cell differentiation and played roles in maintenance of the lineage identity. Importantly, GrA+ Th cells promoted aGVHD-associated morbidity and mortality and contributed to crypt destruction within intestines but were not required for the beneficial graft-versus-leukemia effect. Our data indicate that GrA+ Th cells represent a distinct Th subset and are critical mediators of aGVHD. info:eu-repo/grantAgreement/ES/DGA-FEDER/B29-17R info:eu-repo/grantAgreement/ES/MCIU-AEI/SAF2017-83120-C2-1-R info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 8.315 2020 MEDICINE, RESEARCH & EXPERIMENTAL 16 / 140 = 0.114 2020 Q1 T1 4.099 2020 Medicine (miscellaneous) 2020 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Griesenauer, B. Jiang, H. Adom, D. Mehrpouya-Bahrami, P. Chakravorty, S. Kazemian, M. Imam, T. Srivastava, R. Hayes, T.A. Pardo, J. Universidad de Zaragoza (orcid)0000-0003-0154-0730 Janga, S.C. Paczesny, S. Kaplan, M.H. Olson, M.R. 1011 566 Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Área Inmunología 5, 18 (2020), e124465 [18 pp] JCI insight JCI insight 2379-3708 631860 http://zaguan.unizar.es/record/95754/files/texto_completo.pdf Versión publicada 265723 http://zaguan.unizar.es/record/95754/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:95754 articulos driver 2023-07-06-12:20:45 ARTICLE