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

Eryn Bugbee; A. Wang; Jennifer L. Gommerman

doi:10.3389/fimmu.2023.1188750

August 3, 2023Frontiers in ImmunologyOpen Access

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

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Key Points

To review the mechanisms by which IL-10 receptor signaling attenuates neuroinflammation and evaluate how environmental factors and intestinal microbes modulate this pathway in multiple sclerosis.
Synthesized historical and modern literature investigating IL-10/IL-10R signaling pathways in animal models of multiple sclerosis and in human disease-modifying therapy responses.
Evaluated preclinical and clinical evidence regarding the influence of external environmental exposures and gut microbiota on IL-10 regulation.
Constructed a conceptual mechanistic model linking environmental triggers, IL-10-producing B cells, and central nervous system inflammation.
IL-10/IL-10R signaling consistently suppresses central nervous system neuroinflammation in animal models of multiple sclerosis and correlates with positive responses to disease-modifying therapies.
Specific environmental exposures and intestinal microbial populations directly alter IL-10 and IL-10R activity, influencing disease susceptibility and clinical progression.
IL-10-producing B cells serve as a primary cellular conduit that conveys environmental and microbial cues to mitigate inflammation in the central nervous system.

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Implication

Review uncovers environmental and microbial modulation of the IL-10/IL-10R pathway in multiple sclerosis, indicating B cells transmit external cues to calm central nervous system inflammation.

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.

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Bugbee et al. (2023) studied this question.

synapsesocial.com/papers/6a13069692637892a9a7b1f3 https://doi.org/10.3389/fimmu.2023.1188750

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

Key Points

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Cite This Study

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

Key Points

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Implication

Abstract

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