B cell-derived GABA elicits IL-10+ macrophages to limit anti-tumour immunity
Menée in vitro et à l'aide de modèles murins, cette étude met en évidence un mécanisme par lequel le neurotransmetteur GABA (acide gamma-aminobutyrique) libéré par les lymphocytes B limite la réponse antitumorale du système immunitaire en favorisant la différenciation des monocytes en macrophages anti-inflammatoires sécrétant l'interleukine IL-10
Small, soluble metabolites not only are essential intermediates in intracellular biochemical processes, but can also influence neighbouring cells when released into the extracellular milieu1–3. Here we identify the metabolite and neurotransmitter GABA as a candidate signalling 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 that secrete interleukin-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-tumour 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.