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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.
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Baihao Zhang
Alexis Vogelzang
Michio Miyajima
Nature
Kyoto University
Keio University
RIKEN Center for Integrative Medical Sciences
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Zhang et al. (Wed,) studied this question.
www.synapsesocial.com/papers/69dbd1e27d378569a9836117 — DOI: https://doi.org/10.1038/s41586-021-04082-1
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