The IL-12-STAT4 axis in the pathogenesis of human systemic lupus erythematosus
- PMID: 31762023
- DOI: 10.1002/eji.201948134
The IL-12-STAT4 axis in the pathogenesis of human systemic lupus erythematosus
Abstract
Generation of autoantibodies is a hallmark of systemic lupus erythematosus (SLE). As demonstrated in a number of lupus mouse models, recent evidence suggests that both GC and extrafollicular pathways contribute to the generation of autoantibodies also in human SLE, and that CD11c+ IgD- CD27- (double negative:DN) B cells play a central role in the latter pathway. In this mini-review, the author will first briefly summarize the features of CD11c+ DN B cells in human SLE, and discuss how the IL-12-STAT4 axis might contribute to the generation of autoantibodies in SLE. In addition, various types of CD4+ helper T cell subsets promoting the generation of autoantibodies in SLE will be described, and finally it will be discussed how these recent discoveries contribute to understanding of SLE pathogenesis and treatment of SLE patients.
Keywords: CD11c+ T-bet+ B cells; IL-12; STAT4; T-bet; systemic lupus erythematosus.
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Similar articles
-
Type I Interferon-Activated STAT4 Regulation of Follicular Helper T Cell-Dependent Cytokine and Immunoglobulin Production in Lupus.Arthritis Rheumatol. 2021 Mar;73(3):478-489. doi: 10.1002/art.41532. Epub 2021 Jan 29. Arthritis Rheumatol. 2021. PMID: 33512094 Free PMC article.
-
IL-10 producing regulatory and helper T-cells in systemic lupus erythematosus.Semin Immunol. 2019 Aug;44:101330. doi: 10.1016/j.smim.2019.101330. Epub 2019 Nov 15. Semin Immunol. 2019. PMID: 31735515 Review.
-
Expansion of T follicular helper-T helper 1 like cells through epigenetic regulation by signal transducer and activator of transcription factors.Ann Rheum Dis. 2018 Sep;77(9):1354-1361. doi: 10.1136/annrheumdis-2017-212652. Epub 2018 May 31. Ann Rheum Dis. 2018. PMID: 29853448
-
STAT4 Is Largely Dispensable for Systemic Lupus Erythematosus-like Autoimmune- and Foreign Antigen-Driven Antibody-Forming Cell, Germinal Center, and Follicular Th Cell Responses.Immunohorizons. 2021 Jan 14;5(1):2-15. doi: 10.4049/immunohorizons.2000111. Immunohorizons. 2021. PMID: 33446493 Free PMC article.
-
T follicular helper (Tfh) cells in lupus: Activation and involvement in SLE pathogenesis.Eur J Immunol. 2016 Feb;46(2):281-90. doi: 10.1002/eji.201545760. Eur J Immunol. 2016. PMID: 26614103 Review.
Cited by
-
Aberrant expansion of follicular helper T cell subsets in patients with systemic lupus erythematosus.Front Immunol. 2022 Sep 2;13:928359. doi: 10.3389/fimmu.2022.928359. eCollection 2022. Front Immunol. 2022. PMID: 36119056 Free PMC article.
-
Jak Inhibitors for Treatment of Autoimmune Diseases: Lessons from Systemic Sclerosis and Systemic Lupus Erythematosus.Pharmaceuticals (Basel). 2022 Jul 28;15(8):936. doi: 10.3390/ph15080936. Pharmaceuticals (Basel). 2022. PMID: 36015084 Free PMC article. Review.
-
Genetic polymorphisms in genes involved in the type I interferon system (STAT4 and IRF5): association with Asian SLE patients.Clin Rheumatol. 2024 Aug;43(8):2403-2416. doi: 10.1007/s10067-024-07046-8. Epub 2024 Jul 4. Clin Rheumatol. 2024. PMID: 38963465 Review.
-
Targeting T-bet expressing B cells for therapeutic interventions in autoimmunity.Clin Exp Immunol. 2024 Jul 12;217(2):159-166. doi: 10.1093/cei/uxae036. Clin Exp Immunol. 2024. PMID: 38647337 Free PMC article. Review.
-
Modifying T cell phenotypes using TYK2 inhibitor and its implications for the treatment of systemic lupus erythematosus.RMD Open. 2024 Jun 13;10(2):e003991. doi: 10.1136/rmdopen-2023-003991. RMD Open. 2024. PMID: 38871479 Free PMC article.
References
-
- Tsokos, G. C., Systemic lupus erythematosus. N. Engl. J. Med. 2011. 365: 2110-2121.
-
- Blanco, P., Ueno, H. and Schmitt, N., T follicular helper (Tfh) cells in lupus: activation and involvement in SLE pathogenesis. Eur. J. Immunol. 2016. 46: 281-290.
-
- Arce, E., Jackson, D. G., Gill, M. A., Bennett, L. B., Banchereau, J. and Pascual, V., Increased frequency of pre-germinal center B cells and plasma cell precursors in the blood of children with systemic lupus erythematosus. J. Immunol. 2001. 167: 2361-2369.
-
- Jacobi, A. M., Odendahl, M., Reiter, K., Bruns, A., Burmester, G. R., Radbruch, A.,Valet, G. et al., Correlation between circulating CD27 high plasma cells and disease activity in patients with systemic lupus erythematosus. Arthr. Rheumat. 2003. 48: 1332-1342.
-
- Grammer, A. C., Slota, R., Fischer, R., Gur, H., Girschick, H., Yarboro, C., Illei, G. G. et al., Abnormal germinal center reactions in systemic lupus erythematosus demonstrated by blockade of CD154-CD40 interactions. J. Clin. Invest. 2003. 112: 1506-1520.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous