Faslpr gene dosage tunes the extent of lymphoproliferation and T cell differentiation in lupus

Faslpr gene dosage tunes the extent of lymphoproliferation and T cell differentiation in lupus

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 258(2024) vom: 19. Jan., Seite 109874
1. Verfasser: Bohat, Ritu (VerfasserIn)
Weitere Verfasser: Liang, Xiaofang, Chen, Yanping, Xu, Chunyu, Zheng, Ningbo, Guerrero, Ashley, Hou, Jiakai, Jaffery, Roshni, Egan, Nicholas A, Li, Yaxi, Tang, Yitao, Unsal, Esra, Robles, Adolfo, Chen, Si, Major, Angela M, Elldakli, Hadil, Chung, Sang-Hyuk, Liang, Han, Hicks, M John, Du, Yong, Lin, Jamie S, Chen, Xiqun, Mohan, Chandra, Peng, Weiyi
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2024
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Autoimmune disease FAS Genetics Lupus
Beschreibung
Zusammenfassung:Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Sle1 and Faslpr are two lupus susceptibility loci that lead to manifestations of systemic lupus erythematosus. To evaluate the dosage effects of Faslpr in determining cellular and serological phenotypes associated with lupus, we developed a new C57BL/6 (B6) congenic lupus strain, B6.Sle1/Sle1.Faslpr/+ (Sle1homo.lprhet) and compared it with B6.Faslpr/lpr (lprhomo), B6.Sle1/Sle1 (Sle1homo), and B6.Sle1/Sle1.Faslpr/lpr (Sle1homo.lprhomo) strains. Whereas Sle1homo.lprhomo mice exhibited profound lymphoproliferation and early mortality, Sle1homo.lprhet mice had a lifespan comparable to B6 mice, with no evidence of splenomegaly or lymphadenopathy. Compared to B6 monogenic lupus strains, Sle1homo.lprhet mice exhibited significantly elevated serum ANA antibodies and increased proteinuria. Additionally, Sle1homo.lprhet T cells had an increased propensity to differentiate into Th1 cells. Gene dose effects of Faslpr were noted in upregulating serum IL-1⍺, IL-2, and IL-27. Taken together, Sle1homo.lprhet strain is a new C57BL/6-based model of lupus, ideal for genetic studies, autoantibody repertoire investigation, and for exploring Th1 effector cell skewing without early-age lymphoproliferative autoimmunity
Beschreibung:Date Completed 02.01.2024
Date Revised 10.04.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2023.109874