IL-6/IL-12 superfamily of cytokines and regulatory lymphocytes play critical roles in the etiology and suppression of CNS autoimmune diseases

Cytokines influence cell-fate decisions of naïve lymphocytes and determine outcome of immune responses by transducing signals that regulate the initiation, intensity and duration of immune responses. However, aberrant regulation of physiological levels of cytokines contribute to the development of a...

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Main Authors: Manoj Kumar Yadav, Samara P. Singh, Charles E. Egwuagu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1514080/full
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author Manoj Kumar Yadav
Samara P. Singh
Charles E. Egwuagu
author_facet Manoj Kumar Yadav
Samara P. Singh
Charles E. Egwuagu
author_sort Manoj Kumar Yadav
collection DOAJ
description Cytokines influence cell-fate decisions of naïve lymphocytes and determine outcome of immune responses by transducing signals that regulate the initiation, intensity and duration of immune responses. However, aberrant regulation of physiological levels of cytokines contribute to the development of autoimmune and other inflammatory diseases. The Interleukin 6 (IL-6)/IL-12 superfamily of cytokines have a profound influence on all aspects of host immunity and our focus in this review is on the signaling pathways that mediate their functions, with emphasis on how this enigmatic family of cytokines promote or suppress inflammation depending on the physiological context. We also describe regulatory lymphocyte populations that suppress neuroinflammatory diseases by producing cytokines, such as IL-27 (i27-Breg) or IL-35 (i35-Breg and iTR35). We conclude with emerging immunotherapies like STAT-specific Nanobodies, Exosomes and Breg therapy that ameliorate CNS autoimmune diseases in preclinical studies.
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spelling doaj-art-05ceca3f49d2402a985d9485f2d8b7192025-08-20T03:16:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.15140801514080IL-6/IL-12 superfamily of cytokines and regulatory lymphocytes play critical roles in the etiology and suppression of CNS autoimmune diseasesManoj Kumar YadavSamara P. SinghCharles E. EgwuaguCytokines influence cell-fate decisions of naïve lymphocytes and determine outcome of immune responses by transducing signals that regulate the initiation, intensity and duration of immune responses. However, aberrant regulation of physiological levels of cytokines contribute to the development of autoimmune and other inflammatory diseases. The Interleukin 6 (IL-6)/IL-12 superfamily of cytokines have a profound influence on all aspects of host immunity and our focus in this review is on the signaling pathways that mediate their functions, with emphasis on how this enigmatic family of cytokines promote or suppress inflammation depending on the physiological context. We also describe regulatory lymphocyte populations that suppress neuroinflammatory diseases by producing cytokines, such as IL-27 (i27-Breg) or IL-35 (i35-Breg and iTR35). We conclude with emerging immunotherapies like STAT-specific Nanobodies, Exosomes and Breg therapy that ameliorate CNS autoimmune diseases in preclinical studies.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1514080/fullcytokinesuveitismultiple-sclerosisEAUEAEJAK/STAT
spellingShingle Manoj Kumar Yadav
Samara P. Singh
Charles E. Egwuagu
IL-6/IL-12 superfamily of cytokines and regulatory lymphocytes play critical roles in the etiology and suppression of CNS autoimmune diseases
Frontiers in Immunology
cytokines
uveitis
multiple-sclerosis
EAU
EAE
JAK/STAT
title IL-6/IL-12 superfamily of cytokines and regulatory lymphocytes play critical roles in the etiology and suppression of CNS autoimmune diseases
title_full IL-6/IL-12 superfamily of cytokines and regulatory lymphocytes play critical roles in the etiology and suppression of CNS autoimmune diseases
title_fullStr IL-6/IL-12 superfamily of cytokines and regulatory lymphocytes play critical roles in the etiology and suppression of CNS autoimmune diseases
title_full_unstemmed IL-6/IL-12 superfamily of cytokines and regulatory lymphocytes play critical roles in the etiology and suppression of CNS autoimmune diseases
title_short IL-6/IL-12 superfamily of cytokines and regulatory lymphocytes play critical roles in the etiology and suppression of CNS autoimmune diseases
title_sort il 6 il 12 superfamily of cytokines and regulatory lymphocytes play critical roles in the etiology and suppression of cns autoimmune diseases
topic cytokines
uveitis
multiple-sclerosis
EAU
EAE
JAK/STAT
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1514080/full
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AT charleseegwuagu il6il12superfamilyofcytokinesandregulatorylymphocytesplaycriticalrolesintheetiologyandsuppressionofcnsautoimmunediseases