Journal
SCIENTIFIC REPORTS
Volume 11, Issue 1, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41598-021-84624-9
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Funding
- Ishidsu Shun Memorial Scholarship, Japan
- Tokyo Medical University Research Grant
- AMED from the Ministry of Education, Culture, Sports, Science and Technology, Japan
- Center for Clinical and Translational Research of Kyushu University Hospital
- program for the Strategic Research Foundation at Private Universities
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IL-23, composed of p19 and p40 subunits, plays a critical role in the expansion of Th17 cells. The composite cytokine p19/CD5L activates STAT5 and enhances differentiation into GM-CSF-producing CD4(+) T cells. Deficiency of p19 or CD5L alleviates EAE with reduced frequency of GM-CSF(+)CD4(+) T cells. Serum level of p19/CD5L correlates with clinical symptoms during EAE, suggesting its role as a novel cytokine contributing to EAE development.
Among various cytokines, interleukin (IL)-12 family cytokines have very unique characteristics in that they are composed of two distinct subunits and these subunits are shared with each other. IL-23, one of the IL-12 family cytokines, consists of p19 and p40 subunits, is mainly produced by antigen-presenting cells, and plays a critical role in the expansion and maintenance of pathogenic helper CD4(+) T (Th)17 cells. Since we initially found that p19 is secreted in the culture supernatant of activated CD4(+) T cells, we have further investigated the role of p19. p19 was revealed to associate with CD5 antigen-like (CD5L), which is a repressor of Th17 pathogenicity and is highly expressed in non-pathogenic Th17 cells, to form a composite p19/CD5L. This p19/CD5L was shown to activate STAT5 and enhance the differentiation into granulocyte macrophage colony-stimulating factor (GM-CSF)-producing CD4(+) T cells. Both CD4(+) T cell-specific conditional p19-deficient mice and complete CD5L-deficient mice showed significantly alleviated experimental autoimmune encephalomyelitis (EAE) with reduced frequency of GM-CSF(+)CD4(+) T cells. During the course of EAE, the serum level of p19/CD5L, but not CD5L, correlated highly with the clinical symptoms. Thus, the composite p19/CD5L is a possible novel heterodimeric cytokine that contributes to EAE development with GM-CSF up-regulation.
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