Neuroinflammation: Extinguishing a blaze of T cells

Abstract

Summary Inflammation is a biological process that dynamically alters the surrounding microenvironment, including participating immune cells. As a well‐protected organ surrounded by specialized barriers and with immune privilege properties, the central nervous system (CNS) tightly regulates immune responses. Yet in neuroinflammatory conditions, pathogenic immunity can disrupt CNS structure and function. T cells in particular play a key role in promoting and restricting neuroinflammatory responses, while the inflamed CNS microenvironment can influence and reshape T cell function and identity. Still, the contraction of aberrant T cell responses within the CNS is not well understood. Using autoimmunity as a model, here we address the contribution of CD4 T helper (Th) cell subsets in promoting neuropathology and disease. To address the mechanisms antagonizing neuroinflammation, we focus on the control of the immune response by regulatory T cells (Tregs) and describe the counteracting processes that preserve their identity under inflammatory challenges. Finally, given the influence of the local microenvironment on immune regulation, we address how CNS‐intrinsic signals reshape T cell function to mitigate abnormal immune T cell responses.

Berberine promotes immunological outcomes and decreases neuroinflammation in the experimental model of multiple sclerosis through the expansion of Treg and Th2 cells

“…8 Th2 cells, characterized by the expression of the transcription factor GATA3, which predominantly produces IL-4/IL-10, originally were considered to exert a suppressive role in the pathogenesis of autoimmune demyelination. 9 Additionally, Treg characterized by expression of the transcriptional factor FoxP3 and production of TGF-β and IL-10, has been considered pivotal for controlling autoinflammatory diseases during MS and EAE. 10 IL-27, IL-33, and IL-35 are newly discovered antiinflammatory/immunosuppressive cytokines that both IL-27 and IL-35 belong to anti-inflammatory cytokines of the IL-12 while IL-33 is a new member of the IL-1 superfamily of cytokines.…”

“…Cytokines are important elements of the immunological inflammatory response and deregulated cytokine responses are an undeniable factor in driving CNS inflammation in MS patients 8 . Th2 cells, characterized by the expression of the transcription factor GATA3, which predominantly produces IL‐4/IL‐10, originally were considered to exert a suppressive role in the pathogenesis of autoimmune demyelination 9 . Additionally, Treg characterized by expression of the transcriptional factor FoxP3 and production of TGF‐β and IL‐10, has been considered pivotal for controlling autoinflammatory diseases during MS and EAE 10 …”

Immune status of the murine 22q11.2 deletion syndrome model

“…We found that active EAE using the MOG 35‐55 peptide induced a clinical course of disease in 22qMc that was not different from WT littermates (Figure 4A). The cytokines IL‐17, IFN‐γ, GM‐CSF, and TNF‐α drive the inflammatory phenotype of T helper cells in EAE [27, 28]. Notably, we did not observe any differences in the inflammatory profile of T cells isolated from the spleens or from the CNS of 22qMc and WT littermates at the peak of disease (Fig.…”

An introduction to neuroimmunology

“…T cells have also been identified to be major drivers of neuronal demise in various neurological disease settings including MS. In the next article of the series, Dr. Alvarez and colleagues offer new insights into how CNS‐intrinsic signals reshape T cell function in the context of demyelinating neuroinflammatory diseases such as MS 11 . Many previous MS reviews have focused on how T cells impact CNS‐resident cells.…”

“…T cells have also been identified to be major drivers of neuronal demise in various neurological disease settings including MS. In the next article of the series, Dr. Alvarez and colleagues offer new insights into how CNS-intrinsic signals reshape T cell function in the context of demyelinating neuroinflammatory diseases such as MS. 11 Many previous MS reviews have focused on how T cells impact CNS-resident cells. In contrast, the review by Alvarez and colleagues flips the script and provides a fresh take on how the CNS microenvironment, and astrocytes, in particular, modulate encephalitogenic T cell responses.…”