Browsing by Author "Chakravorty, Srishti"

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    Granzyme A–producing T helper cells are critical for acute graft-versus-host disease
    (American Society for Clinical Investigation, 2020-08-18) Park, Sungtae; Griesenauer, Brad; Jiang, Hua; Adom, Djamilatou; Mehrpouya-Bahrami, Pegah; Chakravorty, Srishti; Kazemian, Majid; Imam, Tanbeena; Srivastava, Rajneesh; Hayes, Tristan A.; Pardo, Julian; Janga, Sarath Chandra; Paczesny, Sophie; Kaplan, Mark H.; Olson, Matthew R.; Microbiology and Immunology, School of Medicine
    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.