Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons

Lima, Kalil Alves de; Rustenhoven, Justin; Mesquita, Sandro Dá; Wall, Morgan; Salvador, Andrea Francesca; Smirnov, Igor; Cebinelli, Guilherme Cesar Martelossi; Mamuladze, Tornike; Baker, Wendy; Papadopoulos, Zachary; Lopes, M. Beatriz S.; Cao, William S.; Xie, Xinmin; Herz, Jasmin; Kipnis, Jonathan

doi:10.1038/s41590-020-0776-4

Cited by 240 publications

(216 citation statements)

References 41 publications

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“…Since meningeal γδ T cells have been identified as well, it is interesting to know the role of γδ T cells in regulating brain functions. Recently, two elegant works by Ribot’s group and Kipnis’ group found that meningeal γδ T cells could secrete IL-17 to regulate short-term memory and anxiety-like behavior, which partially addressed this issue ( 8 , 25 ) ( Figure 1 ).…”

Section: γδ T Cells Interact With the Central Nervous Systemmentioning

confidence: 99%

“…Meningeal γδ T cells are tissue-resident cells expressing C-X-C Motif Chemokine Receptor 6 (CXCR6) and are attracted by chemokine C-X-C Motif Chemokine Ligand 16 (CXCL16), which is highly expressed in dura-resident myeloid cells ( 25 ). They migrate to meninges shortly after birth and are prevalent in dura mater.…”

Section: γδ T Cells Interact With the Central Nervous Systemmentioning

confidence: 99%

“…They migrate to meninges shortly after birth and are prevalent in dura mater. More importantly, they are the major source of IL-17 ( 8 , 25 ). The majority of these meningeal γδ T17 cells are fetal derived Vγ6Vδ1 (the V region of TCR γ chain uses TRGV6 gene and the δ chain uses TRDV1 gene) T cells with canonical identical Vγ6-Jγ1 and Vδ1-Dδ2-Jδ2 chains that can be found in various non-lymphoid tissues ( 8 , 9 , 26 , 27 ).…”

Section: γδ T Cells Interact With the Central Nervous Systemmentioning

confidence: 99%

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γδ T Cells Participating in Nervous Systems: A Story of Jekyll and Hyde

Zhang

Zeng

2021

Front. Immunol.

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γδ T cells are distributed in various lymphoid and nonlymphoid tissues, and act as early responders in many conditions. Previous studies have proven their significant roles in infection, cancer, autoimmune diseases and tissue maintenance. Recently, accumulating researches have highlighted the crosstalk between γδ T cells and nervous systems. In these reports, γδ T cells maintain some physiological functions of central nervous system by secreting interleukin (IL) 17, and neurons like nociceptors can in turn regulate the activity of γδ T cells. Moreover, γδ T cells are involved in neuroinflammation such as stroke and multiple sclerosis. This review illustrates the relationship between γδ T cells and nervous systems in physiological and pathological conditions.

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Section: γδ T Cells Interact With the Central Nervous Systemmentioning

confidence: 99%

Section: γδ T Cells Interact With the Central Nervous Systemmentioning

confidence: 99%

Section: γδ T Cells Interact With the Central Nervous Systemmentioning

confidence: 99%

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γδ T Cells Participating in Nervous Systems: A Story of Jekyll and Hyde

Zhang

Zeng

2021

Front. Immunol.

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“…Most of these pairs were shared by PNS and cortical neurons (107) and only 12 were unique to T-cells and cortical neurons (2 are shown in Fig 6C). Seventy-eight were unique to PNS neurons, and some of these are highlighted in Fig 6C and (Krukowski et al, 2016;Laumet et al, 2019), and CNS cortical neurons, which likely do not come into direct contact with T-cells, but rather communicate through release of factors in the meninges (Androdias et al, 2010;Filiano et al, 2016;Alves de Lima et al, 2020).…”

Section: Ligand-receptor Interactions Between T-cells and Cns And Pnsmentioning

confidence: 99%

Diversity of receptor expression in central and peripheral mouse neurons estimated from single cell RNA sequencing

Wangzhou

Paige

Ray

et al. 2021

Preprint

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Because somatosensory PNS neurons, in particular nociceptors, are specially tuned to be able to detect a wide variety of both exogenous and endogenous signals, it is widely assumed that these neurons express a greater variety of receptor genes. Because cells detect such signals via cell surface receptors, we sought to formally test the hypothesis that PNS neurons might express a broader array of cell surface receptors than CNS neurons using existing single cell RNA sequencing resources from mouse. We focused our analysis on ion channels, G-protein coupled receptors (GPCRS), receptor tyrosine kinase and cytokine family receptors. In partial support of our hypothesis, we found that mouse PNS somatosensory, sympathetic and enteric neurons and CNS neurons have similar receptor expression diversity in families of receptors examined, with the exception of GPCRs and cytokine receptors which showed greater diversity in the PNS. Surprisingly, these differences were mostly driven by enteric and sympathetic neurons, not by somatosensory neurons or nociceptors. Secondary analysis revealed many receptors that are very specifically expressed in subsets of PNS neurons, including some that are unique among neurons for nociceptors. Finally, we sought to examine specific ligand-receptor interactions between T cells and PNS and CNS neurons. Again, we noted that most interactions between these cells are shared by CNS and PNS neurons despite the fact that T cells only enter the CNS under rare circumstances. Our findings demonstrate that both PNS and CNS neurons express an astonishing array of cell surface receptors and suggest that most neurons are tuned to receive signals from other cells types, in particular immune cells.

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“…In these regions, macrophages are the numerically dominant immune population, and have received the most attention 3 . However, recent studies have demonstrated roles for a broad range of immune cells, including T cells, γδ T cells innate lymphoid cells and beyond, in regulating behavior, inflammation and neurological diseases in the brain and at its interfaces 2,4,5 . Recent studies employing single cell technologies (including single‐cell RNA sequencing, CyTOF and flow cytometry) have also revealed B‐cell populations to be present in the meningeal membranes, 2,3 although their function and relevance for neurological health had remained poorly understood.…”

Section: Figurementioning

confidence: 99%