GABA transporter sustains IL-1β production in macrophages

Xia, Yaoyao; He, Fang; Wu, Xiaoyan; Tan, Bie; Chen, Siyuan; Liao, Yuexia; Qi, Ming; Chen, Shuai; Peng, Yuanyi; Yin, Yulong; Ren, Wenkai

doi:10.1126/sciadv.abe9274

Cited by 45 publications

(47 citation statements)

References 61 publications

(77 reference statements)

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“…Specifically, GABA treatment has been reported to reduce IL-6/IL-12 production in macrophages [39] and impaired phagocytosis of macrophages and monocytic cells [40,72]. However, the GABA transporter GAT2 was recently linked to pro-inflammatory IL-1β secretion in peritoneal macrophages [38]. A recent study showed that activation or blockade of GABA-A Rs influenced the phenotypic characteristics of alveolar macrophages towards classical (M1) or alternative (M2) activation, respectively [73].…”

Section: Role Of Gabaergic Signaling In Immune Activation Of Phagocytesmentioning

confidence: 99%

GABAergic signaling by cells of the immune system: more the rule than the exception

Bhandage

Barragán

2021

Cell. Mol. Life Sci.

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Gamma-aminobutyric acid (GABA) is best known as an essential neurotransmitter in the evolved central nervous system (CNS) of vertebrates. However, GABA antedates the development of the CNS as a bioactive molecule in metabolism and stress-coupled responses of prokaryotes, invertebrates and plants. Here, we focus on the emerging findings of GABA signaling in the mammalian immune system. Recent reports show that mononuclear phagocytes and lymphocytes, for instance dendritic cells, microglia, T cells and NK cells, express a GABAergic signaling machinery. Mounting evidence shows that GABA receptor signaling impacts central immune functions, such as cell migration, cytokine secretion, immune cell activation and cytotoxic responses. Furthermore, the GABAergic signaling machinery of leukocytes is implicated in responses to microbial infection and is co-opted by protozoan parasites for colonization of the host. Peripheral GABA signaling is also implicated in inflammatory conditions and diseases, such as type 1 diabetes, rheumatoid arthritis and cancer cell metastasis. Adding to its role in neurotransmission, growing evidence shows that the non-proteinogenic amino acid GABA acts as an intercellular signaling molecule in the immune system and, as an interspecies signaling molecule in host–microbe interactions. Altogether, the data raise the assumption of conserved GABA signaling in a broad range of mammalian cells and diversification of function in the immune system.

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Section: Role Of Gabaergic Signaling In Immune Activation Of Phagocytesmentioning

confidence: 99%

GABAergic signaling by cells of the immune system: more the rule than the exception

Bhandage

Barragán

2021

Cell. Mol. Life Sci.

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“…An increasing number of studies have illustrated the critical roles of GABA transporters (GAT) on health and diseases. Xia et al ( 30 ) showed that GAT2 (SLC6A13) sustained IL-1β production in macrophages, and Ren et al ( 18 ) identified the role of GAT2 in the defense against pathogen infection. This study found that L.lactis reduced GAT2 expression and regulated GABA receptors.…”

Section: Discussionmentioning

confidence: 99%

Effects of Lactococcus lactis on the Intestinal Functions in Weaning Piglets

Xia

et al. 2021

Front. Nutr.

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Post-weaning diarrhea of piglets is associated with gut microbiota dysbiosis and intestinal pathogen infection. Recent studies have shown that Lactococcus lactis (L.lactis) could help suppress pathogen infection. This study aimed to investigate the effects of L.lactis on various factors related to growth and immunity in weaning piglets. The results showed that L.lactis improved the growth performance, regulated the amino acid profile (for example, increasing serum tryptophan and ileal mucosal cystine) and the intestinal GABAergic system (including inhibiting ileal gene expression of SLC6A13, GABAAρ1, π, θ, and γ1, and promoting ileal GABAAα5 expression). L.lactis also modulated intestinal immunity by promoting jejunal interleukin 17, 18, 22, ileal toll-like receptor 2, 5, 6, and myeloid differentiation primary response protein 88 gene expression while inhibiting jejunal interferon-γ and ileal interleukin 22 expressions. L.lactis highly affected the intestinal microbiota by improving the beta diversity of gut microbiota and the relative abundance of Halomonas and Shewanella. In conclusion, L.lactis improved the growth performance and regulated amino acid profiles, intestinal immunity and microbiota in weaning piglets.

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“…Notably, defects in macrophage phenotypic switch, such as the prolonged activation of a pro-inflammatory property in macrophages, are associated with various macrophage-associated diseases ( 117 ). Thus, the significant role of iron in dictating macrophage polarization suggests that iron has potential for affecting the progression of macrophage-associated diseases.…”

Section: Iron In Macrophage-associated Diseasesmentioning

confidence: 99%

Ironing Out the Details: How Iron Orchestrates Macrophage Polarization

Xia

et al. 2021

Front. Immunol.

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Iron fine-tunes innate immune responses, including macrophage inflammation. In this review, we summarize the current understanding about the iron in dictating macrophage polarization. Mechanistically, iron orchestrates macrophage polarization through several aspects, including cellular signaling, cellular metabolism, and epigenetic regulation. Therefore, iron modulates the development and progression of multiple macrophage-associated diseases, such as cancer, atherosclerosis, and liver diseases. Collectively, this review highlights the crucial role of iron for macrophage polarization, and indicates the potential application of iron supplementation as an adjuvant therapy in different inflammatory disorders relative to the balance of macrophage polarization.

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GABA transporter sustains IL-1β production in macrophages

Cited by 45 publications

References 61 publications

GABAergic signaling by cells of the immune system: more the rule than the exception

GABAergic signaling by cells of the immune system: more the rule than the exception

Effects of Lactococcus lactis on the Intestinal Functions in Weaning Piglets

Ironing Out the Details: How Iron Orchestrates Macrophage Polarization

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