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Publication : B cell-derived GABA elicits IL-10<sup>+</sup> macrophages to limit anti-tumour immunity.

First Author  Zhang B Year  2021
Journal  Nature Volume  599
Issue  7885 Pages  471-476
PubMed ID  34732892 Mgi Jnum  J:326181
Mgi Id  MGI:7287939 Doi  10.1038/s41586-021-04082-1
Citation  Zhang B, et al. (2021) B cell-derived GABA elicits IL-10(+) macrophages to limit anti-tumour immunity. Nature 599(7885):471-476
abstractText  Small, soluble metabolites not only are essential intermediates in intracellular biochemical processes, but can also influence neighbouring cells when released into the extracellular milieu(1-3). 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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