Short-Chain Fatty Acid Receptor GPR109 Deficient T Cells Induce Less GVHD

Docampo MD, da Silva MB, Lazrak A, et al. Alloreactive T Cells Deficient of the Short-Chain Fatty Acid Receptor GPR109A Induce Less Graft-Versus-Host Disease. Blood. 2021; (doi: 10.1182/blood.2021010719).

GPR109A, a G-protein-coupled receptor of short-chain fatty acids (SCFAs), is implicated in the development of graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (allo-HCT), researchers report. When SCFAs bind with GPR109A, cellular effects on metabolism or changes in immune function may result. In murine models of allo-HCT and GVHD, GPR109A was the primary receptor for butyrate, an SCFA. Investigators observed that allo-HCT mice receiving T cells from GPR109A knockout mice were substantially less affected by GVHD morbidity and mortality than mice receiving wild type T cells. The findings indicate that GPR109A expression on allo-activated T cells is critical for metabolic homeostasis and expansion, both of which are required for GVHD to develop following allo-HCT, and that alloreactive T cells lacking the receptor induce the complication less often.

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