IL-37 Isoform A Prevents Collagen-Induced Arthritis in Mice by Modulating the Th17/Treg Balance via IL1R8 Receptors
Abstract
:1. Introduction
2. Results
2.1. IL-37a Is Expressed in Peripheral Blood Mononuclear Cells (Pbmcs) from RA Patients and RA-Fibroblast-like Synoviocytes (FLSs) and Is Markedly Upregulated by Tnfα
2.2. IL-37 Isoform A Is Effective in Preventing Collagen-Induced Arthritis and IL1R8 Deficiency Can Diminish the Effect of IL-37a
2.3. IL-37atg Mice Have Lower Levels of Proinflammatory Cytokines in the Plasma and Synovial Tissues
2.4. Th17 Cell Skewing Occurs in the Lymph Nodes of Wild-Type Mice with Collagen-Induced Arthritis (CIA), While the Balance Is Maintained in IL-37a Transgenic Mice with CIA
2.5. IL-37atg Mice Exhibit Reduced Rorc (RAR-Related Orphan Receptor Gamma) mRNA Expression in Lymph Nodes Compared with WT Mice, and IL-37a Suppresses the Naïve CD4+ T Cells Differentiation into Th17 Cells In Vitro
3. Discussion
4. Materials and Methods
4.1. Cell Culture
4.2. Obtaining IL-37atg Mice and IL-37atg, IL1R8-/- Mice
4.3. Collagen-Induced Arthritis (CIA) Induction and Arthritis Assessment
4.4. Real-Time PCR After Extracting RNA
4.5. Histological Analysis
4.6. Micro-CT Detection and Image Analysis
4.7. Immunohistochemistry
4.8. Flow Cytometry
4.9. Th17 Cell Differentiation
4.10. Cytokine Assays
4.11. Transcriptomics and Differentially Expressed Gene (DEG) Analysis
4.12. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A
Gene | Primers | Sequence (5′>3′) |
---|---|---|
IL37a (Human) | Forward | GGGAAACAGAAACCAAAGGA |
Reverse | CCCAGAGTCCAGGACCAGTA | |
IL37b (Human) | Forward | AGCCTCCCCACCATGAATTT |
Reverse | ATTCCCAGAGTCCAGGACCA | |
IL37c (Human) | Forward | AGTGCTGCTTAGAAGACCCG |
Reverse | CCCTTTAGAGACCCCCAGGA | |
IL37d (Human) | Forward | GGGGGAGAACTCAGGAGTGA |
Reverse | ACCTTTGGACCTTCTAAGCAGC | |
IL37e (Human) | Forward | CCCAGTGCTGCTTAGAAGAGA |
Reverse | CCTTTAGAGACCCCCAGGAGA | |
Rorc (Mouse) | Forward | CCGCTGAGAGGGCTTCAC |
Reverse | TGCAGGAGTAGGCCACATTACA | |
Foxp3 (Mouse) | Forward | CCCATCCCCAGGAGTCTTG |
Reverse | ACCATGACTAGGGGCACTGTA | |
Il-17a (Mouse) | Forward | TTTAACTCCCTTGGCGCAAAA |
Reverse | CTTTCCCTCCGCATTGACAC | |
GAPDH (Human) | Forward | CTGACTTCAACAGCGACACC |
Reverse | TAGCCAAATTCGTTGTCATAC | |
Gapdh (Mouse) | Forward | GTGTTCCTACCCCCAATGTGT |
Reverse | ATTGTCATACCAGGAAATGAGCTT |
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Lyu, S.; Fang, Z.; Hu, Y.; Zhang, M.; He, J.; Wang, X.; He, J.; Gao, X.; Wang, H.; Xu, D.; et al. IL-37 Isoform A Prevents Collagen-Induced Arthritis in Mice by Modulating the Th17/Treg Balance via IL1R8 Receptors. Int. J. Mol. Sci. 2024, 25, 12878. https://doi.org/10.3390/ijms252312878
Lyu S, Fang Z, Hu Y, Zhang M, He J, Wang X, He J, Gao X, Wang H, Xu D, et al. IL-37 Isoform A Prevents Collagen-Induced Arthritis in Mice by Modulating the Th17/Treg Balance via IL1R8 Receptors. International Journal of Molecular Sciences. 2024; 25(23):12878. https://doi.org/10.3390/ijms252312878
Chicago/Turabian StyleLyu, Shuyan, Zhengyu Fang, Yiping Hu, Miaomiao Zhang, Jiaxin He, Xiaocheng Wang, Juan He, Xu Gao, Hongli Wang, Damo Xu, and et al. 2024. "IL-37 Isoform A Prevents Collagen-Induced Arthritis in Mice by Modulating the Th17/Treg Balance via IL1R8 Receptors" International Journal of Molecular Sciences 25, no. 23: 12878. https://doi.org/10.3390/ijms252312878
APA StyleLyu, S., Fang, Z., Hu, Y., Zhang, M., He, J., Wang, X., He, J., Gao, X., Wang, H., Xu, D., & Wang, Q. (2024). IL-37 Isoform A Prevents Collagen-Induced Arthritis in Mice by Modulating the Th17/Treg Balance via IL1R8 Receptors. International Journal of Molecular Sciences, 25(23), 12878. https://doi.org/10.3390/ijms252312878