IL-15-secreting γδT cells induce memory T cells in experimental allergic encephalomyelitis (EAE) mice

Wang, Xiaoqian; Wei, Yinxiang; Liu, Xiaoling; Chen, Xing; Han, Gencheng; Chen, Guojiang; Hou, Chunmei; Dambuza, Ivy M.; Shen, Beifen; Li, Yan; Xiao, He; Wang, Renxi

doi:10.1016/j.molimm.2015.04.021

Cited by 10 publications

(10 citation statements)

References 39 publications

(44 reference statements)

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“…CNS inflammation is associated with altered expression of HSPs, which may function as targets in the development of the chronic disease. Interestingly, IL-15-producing gd T (gdT15) cells, another subset of gd T cell, were recently discovered; however, whether these cells produce other proinflammatory cytokines in EAE is not well elucidated (94).…”

Section: Gd T Cells In Cns Diseases Multiple Sclerosis and Experimentsmentioning

confidence: 99%

The Role of Gamma-Delta T Cells in Diseases of the Central Nervous System

Zhang

et al. 2020

Front. Immunol.

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Gamma-delta (gd) T cells are a subset of T cells that promote the inflammatory responses of lymphoid and myeloid lineages, and are especially vital to the initial inflammatory and immune responses. Given the capability to connect crux inflammations of adaptive and innate immunity, gd T cells are responsive to multiple molecular cues and can acquire the capacity to induce various cytokines, such as GM-CSF, IL-4, IL-17, IL-21, IL-22, and IFN-g. Nevertheless, the exact mechanisms responsible for gd T cell proinflammatory functions remain poorly understood, particularly in the context of the central nervous system (CNS) diseases. CNS disease, usually leading to irreversible cognitive and physical disability, is becoming a worldwide public health problem. Here, we offer a review of the neuroinflammatory and immune functions of gd T cells, intending to understand their roles in CNS diseases, which may be crucial for the development of novel clinical applications.

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Section: Gd T Cells In Cns Diseases Multiple Sclerosis and Experimentsmentioning

confidence: 99%

The Role of Gamma-Delta T Cells in Diseases of the Central Nervous System

Zhang

et al. 2020

Front. Immunol.

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“…IL-2, which is known to suppress Th17 cells ( 63 ), promotes γδT17 cells generation, as Il2 −/− and Cd25 −/− mice selectively reduced the frequency of γδT17 cells ( 64 ). Interestingly, the new subset of IL-15-producing γδ T cells (γδT15) was recently identified in EAE ( 65 ). γδT15 cells suggested to enhance tissue inflammation in EAE by enhancing the functions of CD44 hi memory T and Th17 cells ( 65 ).…”

Section: Proinflammatory Cytokines That Induce Il-17 From γδ T Cellsmentioning

confidence: 99%

“…Interestingly, the new subset of IL-15-producing γδ T cells (γδT15) was recently identified in EAE ( 65 ). γδT15 cells suggested to enhance tissue inflammation in EAE by enhancing the functions of CD44 hi memory T and Th17 cells ( 65 ). However, whether these γδT15 cells express other inflammatory cytokines, such as IL-17 and GM-CSF, are not clear.…”

Section: Proinflammatory Cytokines That Induce Il-17 From γδ T Cellsmentioning

confidence: 99%

The Emerging Roles of Gamma–Delta T Cells in Tissue Inflammation in Experimental Autoimmune Encephalomyelitis

2016

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γδ (gamma–delta) T cells, a small population of unconventional T cells, have been found in central nervous system lesions of multiple sclerosis (MS) patients, but their function in disease activity is not clearly understood. Previous studies in experimental autoimmune encephalomyelitis (EAE) were inconsistent in identifying their specific roles in suppressing or promoting disease pathogenesis. Emerging advancements in the biology of γδ T cells especially in the context of their being the major initial producers of IL-17, suggested their crucial role in pathogenesis of EAE. In addition, γδ T cells express high levels of IL-23R and IL-1R, which further enhance their effector functions in the pathogenesis of EAE. Nonetheless, activated heterogeneous γδ T cells display functional dichotomy, which is crucial in determining the outcomes of tissue inflammation in EAE. In this review, we discussed recent advances in understanding the biology of γδ T cells in tissue inflammation as well as their roles in suppressing or promoting the development of EAE.

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“…IL-15 up-regulation is observed in serum and cerebrospinal fluid of MS patients 41 42 and mice of experimental autoimmune encephalomyelitis (EAE) 2 . IL-15 contributes to the tissue damages caused by CD8 + T cells and Th17 cells in MS patients and EAE models 45 46 . In addition, IL-15 is found to actively modulate microglial reactivity, co-activating the MAPK and NF-κB pathways, controlling additional cytokine and chemokine release 38 .…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, IL-15 produced by astrocytes can induce CD8 + T cell activation to contribute to tissue damage during MS pathogenesis 45 . γδT cell-producing IL-15 also induces memory T cells which transform into pathogenic Th17 cells in EAE mice, so IL-15 could be pathogenic in EAE 46 .…”

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confidence: 99%

An activation-induced IL-15 isoform is a natural antagonist for IL-15 function

Zhao

Zhang

et al. 2016

Sci Rep

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Interleukin 15 (IL-15) expression induces the secretion of inflammatory cytokines, inhibits the apoptosis of activated T cells and prolongs the survival of CD8+ memory T cells. Here we identified an IL-15 isoform lacking exon-6, IL-15ΔE6, generated by alternative splicing events of activated immune cells, including macrophages and B cells. In vitro study showed that IL-15ΔE6 could antagonize IL-15-mediated T cell proliferation. The receptor binding assay revealed that IL-15ΔE6 could bind to IL-15Rα and interfere with the binding between IL-15 and IL-15Rα. Over-expression of IL-15ΔE6 in the murine EAE model ameliorated the EAE symptoms of the mice. The clinical scores were significantly lower in the mice expressing IL-15ΔE6 than the control mice and the mice expressing IL-15. The inflammation and demyelination of the EAE mice expressing IL-15ΔE6 were less severe than the control group. Furthermore, flow cytometry analysis demonstrated that IL-15ΔE6 expression reduced the percentages of inflammatory T cells in the spleen and spinal cord, and inhibited the infiltration of macrophages to the CNS. Our results demonstrated that IL-15ΔE6 could be induced during immune activation and function as a negative feedback mechanism to dampen IL-15-mediated inflammatory events.

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IL-15-secreting γδT cells induce memory T cells in experimental allergic encephalomyelitis (EAE) mice

Cited by 10 publications

References 39 publications

The Role of Gamma-Delta T Cells in Diseases of the Central Nervous System

The Role of Gamma-Delta T Cells in Diseases of the Central Nervous System

The Emerging Roles of Gamma–Delta T Cells in Tissue Inflammation in Experimental Autoimmune Encephalomyelitis

An activation-induced IL-15 isoform is a natural antagonist for IL-15 function

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