The minor allele rs2295613(A), protective against systemic lupus erythematosus, makes a differential contribution to the activity of the SLAMF1 gene promoter in T helpers and in regulatory T lymphocytes

Uvarova, A.N.; Putlyaeva, L.V.; Zheremyan, E.A.; Stasevich, E.M.; Murashko, M.M.; Bogomolova, E.A.; Korneev, K.V.; Demin, D.E.; Schwartz, A.M.; Kuprash, D.V.

Авторы: Uvarova A.N., Putlyaeva L.V., Zheremyan E.A., Stasevich E.M., Murashko M.M., Bogomolova E.A., Korneev K.V., Demin D.E., Schwartz A.M., Kuprash D.V.
Журнал: Медицинская иммунология
Том: 27
Номер: 3
Год издания: 2025
Первая страница: 677
Последняя страница: 684
DOI: 10.15789/1563-0625-tma-3153
Аннотация: SLAMF1 (CD150) is a receptor expressed on various hematopoietic cells and involved inthe pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). This disorder is a chronicautoimmune inflammatory disease characterized by dysregulation of B lymphocytes, production of a largenumber of autoantibodies, and various abnormalities in immune regulation, such as changes in the numberand functions of T helper cells and T regulatory (Treg) lymphocytes. Expression of SLAMF1 on T helper cellsand B lymphocytes is increased in patients with active SLE. Impaired interaction of SLAMF1 receptors on Tand B lymphocytes reduces the production of IL-6 and differentiation of plasmablasts in SLE. In the presentwork, we performed a functional analysis of single nucleotide promoter polymorphisms rs2295614(A>T)and rs2295613(G>A) of the SLAMF1 gene in the models of T-regulatory lymphocytes (MT-2 cell line) andT helpers (Jurkat cell line). Previously, an association of the rs2295614(A)/rs2295613(G) haplotype with therisk of developing SLE was shown, and it was also demonstrated that the risk haplotype in the promoter regionof the SLAMF1 gene increases promoter activity in the Jurkat T cell line. Using reporter analysis, we haveshown that the activity of the SLAMF1 promoter containing the minor variant rs2295613(A) increases in MT-2cells and decreases in Jurkat cells. Based on the analysis of transcriptomes of these cell lines, we suggest thatsuch a differential effect of the protective minor rs2295613(A) variant on promoter activity may be mediatedby differential binding of transcription factors: activating MYC/MAX heterodimer in MT-2 cells and repressorMAX/MXD4 in Jurkat cells. Furthermore, both the increased expression of SLAMF1 in regulatory T cellsand its decreased expression in T helper cells are likely to impact SLE pathogenesis similarly. These changescould reduce the efficiency of activating signal transmission from T helper cells to B lymphocytes, therebyweakening the autoreactive response of B lymphocytes. Thus, we propose a molecular mechanism mediatingthe protective role of the minor rs2295613(A) allele in the development of SLE.
Добавил в систему: Путляева Лидия Викторовна

	ИСТИНА	Войти в систему Регистрация
	Интеллектуальная Система Тематического Исследования НАукометрических данных
	Главная Поиск Статистика О проекте Помощь

ИСТИНА

Интеллектуальная Система Тематического Исследования НАукометрических данных

The minor allele rs2295613(A), protective against systemic lupus erythematosus, makes a differential contribution to the activity of the SLAMF1 gene promoter in T helpers and in regulatory T lymphocytesстатья

Прикрепленные файлы