Granzyme A-producing T helper cells are critical for acute graft-versus-host disease

Park, S. ; 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) ; Janga, S.C. ; Paczesny, S. ; Kaplan, M.H. ; Olson, M.R.

Resumen: 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.

Idioma: Inglés

DOI: 10.1172/jci.insight.124465

Año: 2020

Publicado en: JCI insight 5, 18 (2020), e124465 [18 pp]
ISSN: 2379-3708

Factor impacto JCR: 8.315 (2020)

Categ. JCR: MEDICINE, RESEARCH & EXPERIMENTAL rank: 16 / 140 = 0.114 (2020) - Q1 - T1

Factor impacto SCIMAGO: 4.099 - Medicine (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA-FEDER/B29-17R
Financiación: info:eu-repo/grantAgreement/ES/MCIU-AEI/SAF2017-83120-C2-1-R

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Inmunología (Dpto. Microb.Ped.Radio.Sal.Pú.)