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

Bhandage, Amol K.; Barragán, Antonio

doi:10.1007/s00018-021-03881-z

Cited by 63 publications

(45 citation statements)

References 134 publications

(200 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1e ). Consistent with the previous findings on the GABA-R expression profile in immune cells 14 . T eff cells express a selected group of GABA-R subunits.…”

Section: Resultssupporting

confidence: 93%

“…In line with earlier studies 14 , we have found that Teff cells express various subunits of GABAA receptor (GABAA-R) (Fig. 1f).…”

Section: Gab Can Serve As An Autocrine Signaling Metabolite That Regu...supporting

confidence: 92%

“…Interaction between the two systems coordinates their sensory functions to ensure organismal homeostasis and survival 24,25 26 27 . Immune cells and neurons can communicate with each other through a group of shared ligand molecules and receptors, including the neurotransmitter GABA and its receptors 14,28 . Beyond mediating intersystem communication between the immune and nervous system, growing evidence suggests that GABA can also act as a paracrine signaling molecule mediating intrasystem communication to regulate immune response 29 .…”

Section: Discussionmentioning

confidence: 99%

“…One recent study has found that B cells can produce GABA and suppress anti-tumor immunity through paracrine modulation of intratumoral macrophages and CD8 + T cells 30 . Also, GABA in macrophages has been implicated as an intracellular metabolite with a pro-inflammatory function 14 . Here we show that GAB (the biochemical form of GABA at physiological pH) is one of the most abundant metabolites in T cells and promotes inflammation through modulating T cell proliferation and differentiation.…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

γ-aminobutyrate (GAB) functions as a bioenergetic and signaling gatekeeper to control T cell inflammation

Kang

Liu

Wang

et al. 2022

Preprint

View full text Add to dashboard Cite

gamma Aminobutyrate (GAB) is the biochemical form of gamma aminobutyric acid (GABA) at physiological pH and functions as an essential neurotransmitter in the vertebrate central nervous system (CNS). Growing evidence suggests that GAB may also mediate intercellular communications to shape various physiological processes, including immune response. Beyond acting as a paracrine signaling molecule, how GAB metabolism is controlled to exert many distinct functions remains elusive. By an integrated analysis of the extracellular metabolome, stable isotope traced metabolic pathway analysis, and metabolic transcriptome, we revealed that GAB is one of the most abundant metabolites produced through glutamine and arginine catabolism in CD4+ T help 17 (TH17) and induced T regulatory (iTreg) cells. GAB functions as a bioenergetic and signaling gatekeeper by reciprocally controlling pro inflammatory TH17 cell and anti inflammatory iTreg cell differentiation through distinct mechanisms. The expression of 4 aminobutyrate aminotransferase (ABAT) funnels GAB, as an anaplerotic substrate, into the TCA cycle to maximize carbon allocation in promoting TH17 cell differentiation. By contrast, the absence of ABAT activities in iTreg cells enables GAB exporting to the extracellular environment and acting as an autocrine signaling metabolite to promote iTreg cell differentiation. Accordingly, genetic or pharmacological ablation of ABAT activity in T cells confers protection against experimental autoimmune encephalomyelitis (EAE) pathogenic progression. Conversely, genetic ablation of GABA(A) receptor in T cells deteriorates EAE pathogenic progression. Collectively, our results suggest that the cell-autonomous control exerted by GAB on CD4+ T cell is bimodal and consists of the sequential action of two discrete processes, ABAT dependent mitochondrial anaplerosis and the receptor-dependent autocrine signaling response, both of which are required for a properly controlled T cell mediated inflammation.

show abstract

“…1e ). Consistent with the previous findings on the GABA-R expression profile in immune cells 14 . T eff cells express a selected group of GABA-R subunits.…”

Section: Resultssupporting

confidence: 93%

“…In line with earlier studies 14 , we have found that Teff cells express various subunits of GABAA receptor (GABAA-R) (Fig. 1f).…”

Section: Gab Can Serve As An Autocrine Signaling Metabolite That Regu...supporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

γ-aminobutyrate (GAB) functions as a bioenergetic and signaling gatekeeper to control T cell inflammation

Kang

Liu

Wang

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Mammalian and fish skin share protective activities against environments that are rich in infectious agents. Fish epidermis is endowed with an extrinsic barrier consisting of a mucus layer and antimicrobial peptides [92]. Recent findings point to the mechanisms through which pathogens interact with each other on the skin and the signaling systems that mediate the communication between the immune system and skin-associated pathogens.…”

Section: Neuro Mast Cell Crosstalk In the Skinmentioning

confidence: 99%

Expression of the Antimicrobial Peptide Piscidin 1 and Neuropeptides in Fish Gill and Skin: A Potential Participation in Neuro-Immune Interaction

et al. 2022

View full text Add to dashboard Cite

Antimicrobial peptides (AMPs) are found widespread in nature and possess antimicrobial and immunomodulatory activities. Due to their multifunctional properties, these peptides are a focus of growing body of interest and have been characterized in several fish species. Due to their similarities in amino-acid composition and amphipathic design, it has been suggested that neuropeptides may be directly involved in the innate immune response against pathogen intruders. In this review, we report the molecular characterization of the fish-specific AMP piscidin1, the production of an antibody raised against this peptide and the immunohistochemical identification of this peptide and enkephalins in the neuroepithelial cells (NECs) in the gill of several teleost fish species living in different habitats. In spite of the abundant literature on Piscidin1, the biological role of this peptide in fish visceral organs remains poorly explored, as well as the role of the neuropeptides in neuroimmune interaction in fish. The NECs, by their role as sensors of hypoxia changes in the external environments, in combination with their endocrine nature and secretion of immunomodulatory substances would influence various types of immune cells that contain piscidin, such as mast cells and eosinophils, both showing interaction with the nervous system. The discovery of piscidins in the gill and skin, their diversity and their role in the regulation of immune response will lead to better selection of these immunomodulatory molecules as drug targets to retain antimicrobial barrier function and for aquaculture therapy in the future.

show abstract

Microglia heterogeneity in health and disease

Dadwal,

Heneka

2023

FEBS Open Bio

View full text Add to dashboard Cite

Microglia, the resident immune cells of the central nervous system (CNS), have received significant attention due to their critical roles in maintaining brain homeostasis and mediating cerebral immune responses. Understanding the origin of microglia has been a subject of great interest, and emerging evidence suggests that microglia consist of multiple subpopulations with unique molecular and functional characteristics. These subpopulations of microglia may exhibit specialized roles in response to different environmental cues as in disease conditions. The newfound understanding of microglial heterogeneity has significant implications for elucidating their roles in both physiological and pathological conditions. In the context of disease, microglia have been studied rigorously as they play a very important role in neuroinflammation. Dysregulated microglial activation and function contribute to chronic inflammation. Further exploration of microglial heterogeneity and their interactions with other cell types in the CNS will undoubtedly pave the way to novel therapeutic strategies targeting microglia‐mediated pathologies. In this review, we discuss the latest advances in the field of microglia research, focusing specifically on the origin and subpopulations of microglia, the populations of microglia types in the brains of patients with neurodegenerative diseases, and how microglia are regulated in the healthy CNS.

show abstract

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

Cited by 63 publications

References 134 publications

γ-aminobutyrate (GAB) functions as a bioenergetic and signaling gatekeeper to control T cell inflammation

γ-aminobutyrate (GAB) functions as a bioenergetic and signaling gatekeeper to control T cell inflammation

Expression of the Antimicrobial Peptide Piscidin 1 and Neuropeptides in Fish Gill and Skin: A Potential Participation in Neuro-Immune Interaction

Microglia heterogeneity in health and disease

Contact Info

Product

Resources

About