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Review
. 2023 Aug 3:14:1188750.
doi: 10.3389/fimmu.2023.1188750. eCollection 2023.

Under the influence: environmental factors as modulators of neuroinflammation through the IL-10/IL-10R axis

Eryn Bugbee  1 , Angela A Wang  1 , Jennifer L Gommerman  1
Affiliations
Review

Under the influence: environmental factors as modulators of neuroinflammation through the IL-10/IL-10R axis

Eryn Bugbee et al. Front Immunol. .

Abstract

The IL-10/IL-10 receptor (IL-10R) axis plays an important role in attenuating neuroinflammation in animal models of Multiple Sclerosis (MS) and increased IL-10 has been associated with a positive response to MS disease modifying therapy. Because environmental factors play an important role in MS susceptibility and disease course, identification of environmental factors that impact the IL-10/IL-10R axis has therapeutic potential. In this review, we provide historical and updated perspectives of how IL-10R signaling impacts neuroinflammation, discuss environmental factors and intestinal microbes with known impacts on the IL-10/IL-10R axis, and provide a hypothetical model for how B cells, via their production of IL-10, may be important in conveying environmental "information" to the inflamed central nervous system.

Keywords: B cells; IL-10; IL-10R; central nervous system; environmental factors; experimental autoimmune encephalomyelitis; multiple sclerosis.

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Conflict of interest statement

JG is receiving reagents from Novartis and Roche to study the role of B cells in MS. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The IL-10/IL-10R Signaling pathway. IL-10 binding to its heterodimeric receptor leads to the phosphorylation of STAT3 by JAK1 and Tyk2. Upon phosphorylation, STAT3 translocates to the nucleus where it binds to STAT3-binding elements and activates the transcription of target genes. STAT3 is responsible for activating the transcription of several IL-10 responsive genes including SOCS3, Bcl3, and Ddit4. Tyk2, Tyrosine kinase 2; JAK1, Janus kinase 1; STAT3, Signal transducer and activator of transcription 3; SOCS3, Suppressor of cytokine signaling 3; DDIT4, DNA damage-inducible transcript 4.
Figure 2
Figure 2
Environmental influences on IL-10-producing B cells. (A) Dietary patterns influence gut microbiota composition. A healthy microbiota and/or its associated diet-derived metabolites can promote the development of IL-10 producing commensal-reactive B cells and IgA+ plasma cells. (B) UV exposure from sunlight, which is influenced by geographical location, changes Vitamin D availability that upon metabolism promotes IL-10 production by lymphocytes. (C) EBV latently infected B cells produce viral homologs of IL-10 that compete with endogenous IL-10 for IL10R binding. Viral IL-10 homologues are less efficient than endogenous IL-10 at triggering downstream signaling.
See this image and copyright information in PMC

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