MOR106 alleviates inflammation in mice with atopic dermatitis by blocking the JAK2/STAT3 signaling pathway and inhibiting IL-17C-mediated Tfh cell differentiation.
- Author:
Limin TIAN
1
;
Xiaohui HUYAN
1
;
Sen YANG
1
;
Mengjie WANG
2
;
Yuenan YANG
3
Author Information
1. Dermatology & STD Department, First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, BaoTou 014010, China.
2. Baotou Medical College, Inner Mongolia University of Science and Technology, BaoTou 014010, China.
3. Dermatology & STD Department, First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, BaoTou 014010, China. *Corresponding author, E-mail: haoyongjie163@163.com.
- Publication Type:Journal Article
- MeSH:
Animals;
Mice;
Dermatitis, Atopic/drug therapy*;
Interleukin-17;
T Follicular Helper Cells;
Janus Kinase 2;
Dinitrochlorobenzene;
Inflammation;
Cell Differentiation;
Signal Transduction
- From:
Chinese Journal of Cellular and Molecular Immunology
2024;40(1):26-32
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the significance of interleukin-17C(IL-17C)-mediated follicular helper T cell (Tfh) differentiation in atopic dermatitis (AD) model. Methods BALB/c mice were divided into control group, AD model group, low-dose MOR106 (anti-IL-17C huIgG1)(MDR106-L)treatment group and high-dose MOR106 (MOR106-H) treatment group, 8 mice in each group. Except for the control group, all the other groups were treated with 2, 4- dinitrochlorobenzene (DNCB) to establish AD models. The low-dose and high-dose MOR106 groups were treated with 5 mg/kg or 10 mg/kg MOR106 respectively. The differentiation of Tfh cell subsets in peripheral blood of mice was analyzed by flow cytometry, and the expression of Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3) signal pathway protein in skin tissue was detected by Western blot analysis. Results Compared with the control group, the dermatitis severity score, mass difference between two ears, spleen mass and spleen index of DNCB group increased significantly, while those of MOR106-L group and MOR106-H group decreased significantly. Compared with the control group, the Tfh subgroup of AD mice showed deregulated differentiation, resulting in a significant increase in the percentage of CD4+CXCR5+IFN-γ+Tfh1 cells, CD4+CXCR5+IL-17A+Tfh17 and CD4+CXCR5+IL-21+Tfh21 cells, and a significant decrease in the percentage of CD4+CXCR5+IL-10+Tfh10 cells and CD4+CXCR5+FOXP3+Tfr cells in peripheral blood. The protein levels of phosphorylated JAK2(p-JAK2) and p-STAT3 were significantly increased. MOR106 effectively reversed these changes of Tfh1, Tfh10, Tfh17, Tfh21 and Tfr cells in peripheral blood of AD mice. Compared with AD group, the levels of p-JAK2 and p-STAT3 protein in low-dose and high-dose MOR106 treatment groups decreased significantly. Conclusion MOR106 can reduce the inflammatory response of AD mice by blocking JAK2/STAT3 signaling pathway and inhibiting the differentiation of Tfh cells mediated by IL-17C.
