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A novel cytokine consisting of the p40 and EBI3 subunits suppresses experimental autoimmune arthritis via reciprocal regulation of Th17 and Treg cells
- Source :
- Cellular and Molecular Immunology
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- ObjectiveThe interleukin (IL)-12 cytokine family is closely related to the development of T helper cells, which are responsible for autoimmune disease enhancement or suppression. IL-12 family members are generally heterodimers and share three α-subunits (p35, p19, and p28) and two β-subunits (p40 and EBI3). However, a β-sheet p40 homodimer has been shown to exist and antagonize IL-12 and IL-23 signaling1. Therefore, we assumed the existence of a p40-EBI3 heterodimer in nature and sought to investigate its role in immune regulation.MethodsThe presence of the p40-EBI3 heterodimer was confirmed by ELISA, immunoprecipitation, and western blotting. A p40-EBI3 vector and p40-EBI3-Fc protein were synthesized to confirm the immunological role of this protein in mice with collagen-induced arthritis (CIA). The anti-inflammatory effects of p40-EBI3 were analyzed with regard to clinical, histological, and immune cell-regulating features in mice with CIA.ResultsClinical arthritis scores and the expression levels of proinflammatory cytokines (e.g., IL-17, IL-1β, IL-6, and TNF-α) were significantly attenuated in p40-EBI3-overexpressing and p40-EBI3-Fc-treated mice with CIA compared to vehicle-treated mice with CIA. Structural joint damage and vessel formation-related gene expression were also reduced by p40-EBI3 heterodimer treatment. In vitro, the p40-EBI3-Fc protein significantly suppressed the differentiation of Th17 cells and reciprocally induced CD4+CD25+Foxp3+(regulatory T) cells. p40-EBI3 also inhibited osteoclast formation in a concentration-dependent manner.ConclusionIn this study, p40-EBI3 ameliorated proinflammatory conditions both in vivo and in vitro. We propose that p40-EBI3 is a novel anti-inflammatory cytokine involved in suppressing the immune response through the expansion of Treg cells and suppression of Th17 cells and osteoclastogenesis.
- Subjects :
- regulatory T cell
Regulatory T cell
medicine.medical_treatment
Immunology
Arthritis
Autoimmunity
p40-EBI3
T-Lymphocytes, Regulatory
Article
Autoimmune Diseases
Proinflammatory cytokine
Minor Histocompatibility Antigens
Mice
Immune system
Autoimmune disease
cytokine
medicine
Animals
Immunology and Allergy
IL-2 receptor
Rheumatoid arthritis
Receptors, Cytokine
Chemistry
FOXP3
hemic and immune systems
EBI3
medicine.disease
Arthritis, Experimental
Interleukin-12
Cell biology
Infectious Diseases
medicine.anatomical_structure
Cytokine
Cytokines
Th17 Cells
Subjects
Details
- ISSN :
- 20420226 and 16727681
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- Cellular & Molecular Immunology
- Accession number :
- edsair.doi.dedup.....a30b331f049fb2f77d040ba33e998318