B cell-derived GABA elicits IL-10+ macrophages and limits anti-tumor immunity

ABSTRACT: Small, soluble metabolites are not only essential intermediates in intracellular biochemical processes, but can also influence neighboring cells when released into the extracellular milieu. Here, we identify the metabolite and neurotransmitter GABA as a candidate signaling molecule synthesized and secreted by activated B cells and plasma cells. We show that B cell-derived GABA promotes monocyte differentiation into anti-inflammatory macrophages which secrete IL-10 and inhibit CD8+ T cell killer function. In mice, B cell deficiency or B cell-specific inactivation of the GABA generating enzyme GAD67 enhances anti-tumor responses. Our study reveals that in addition to cytokines and membrane proteins, small metabolites derived from B lineage cells have immunoregulatory functions, which may be pharmaceutical targets allowing fine-tuning of immune responses.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Bone Marrow

SUBMITTER: Midy Wu  

LAB HEAD: Sidonia Fagarasan

PROVIDER: PXD028403 | Pride | 2021-11-15

REPOSITORIES: Pride