000095754 001__ 95754
000095754 005__ 20230706131408.0
000095754 0247_ $$2doi$$a10.1172/jci.insight.124465
000095754 0248_ $$2sideral$$a120192
000095754 037__ $$aART-2020-120192
000095754 041__ $$aeng
000095754 100__ $$aPark, S.
000095754 245__ $$aGranzyme A-producing T helper cells are critical for acute graft-versus-host disease
000095754 260__ $$c2020
000095754 5060_ $$aAccess copy available to the general public$$fUnrestricted
000095754 5203_ $$aAcute 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.
000095754 536__ $$9info:eu-repo/grantAgreement/ES/DGA-FEDER/B29-17R$$9info:eu-repo/grantAgreement/ES/MCIU-AEI/SAF2017-83120-C2-1-R
000095754 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000095754 590__ $$a8.315$$b2020
000095754 591__ $$aMEDICINE, RESEARCH & EXPERIMENTAL$$b16 / 140 = 0.114$$c2020$$dQ1$$eT1
000095754 592__ $$a4.099$$b2020
000095754 593__ $$aMedicine (miscellaneous)$$c2020$$dQ1
000095754 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000095754 700__ $$aGriesenauer, B.
000095754 700__ $$aJiang, H.
000095754 700__ $$aAdom, D.
000095754 700__ $$aMehrpouya-Bahrami, P.
000095754 700__ $$aChakravorty, S.
000095754 700__ $$aKazemian, M.
000095754 700__ $$aImam, T.
000095754 700__ $$aSrivastava, R.
000095754 700__ $$aHayes, T.A.
000095754 700__ $$0(orcid)0000-0003-0154-0730$$aPardo, J.$$uUniversidad de Zaragoza
000095754 700__ $$aJanga, S.C.
000095754 700__ $$aPaczesny, S.
000095754 700__ $$aKaplan, M.H.
000095754 700__ $$aOlson, M.R.
000095754 7102_ $$11011$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Inmunología
000095754 773__ $$g5, 18 (2020), e124465 [18 pp]$$pJCI insight$$tJCI insight$$x2379-3708
000095754 8564_ $$s631860$$uhttps://zaguan.unizar.es/record/95754/files/texto_completo.pdf$$yVersión publicada
000095754 8564_ $$s265723$$uhttps://zaguan.unizar.es/record/95754/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000095754 909CO $$ooai:zaguan.unizar.es:95754$$particulos$$pdriver
000095754 951__ $$a2023-07-06-12:20:45
000095754 980__ $$aARTICLE