| 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. |
