biostudies-literatureUnknown11(1)Hasegawa HCenter for Clinical and Translational Research of Kyushu University Hospitala program for the Strategic Research Foundation at Private Universities from the Ministry of Education, Culture, Sports, Science and Technology, JapanIshidsu Shun Memorial Scholarship, JapanTokyo Medical University Research GrantGrants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, JapanAMED from the Ministry of Education, Culture, Sports, Science and Technology, JapanAmong 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.Scientific reports5266https://www.ebi.ac.uk/biostudies/studies/S-EPMC7933155biostudies-literatureIL-23p19 and CD5 antigen-like form a possible novel heterodimeric cytokine and contribute to experimental autoimmune encephalomyelitis development.PMC7933155Hasegawa HInoue SXu MMiyazaki TOrii NKatahira YMizoguchi IYoneto TYoshimoto TfalseIL-23p19 and CD5 antigen-like form a possible novel heterodimeric cytokine and contribute to experimental autoimmune encephalomyelitis 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.2021-01-01T00:00:00Z2021 Mar2026-05-01T05:54:30.423Z2021-03-09T08:17:03ZS-EPMC79331553366437110.1038/s41598-021-84624-9