B cell-derived GABA elicits IL-10(+) macrophages to limit anti-tumour immunity

Article

关键词: TUMOR-ASSOCIATED MACROPHAGES;    GAMMA-AMINOBUTYRIC-ACID;    T-CELLS;    MOUSE;    IMMUNOMETABOLISM;    AUTOIMMUNITY;    METABOLISM;    MECHANISMS;    INHIBITION;    REVEALS;   

DOI  :  10.1038/s41586-021-04082-1

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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