Faslpr Gene Dosage Tunes the Extent of Lymphoproliferation and T Cell Differentiation in Lupus

Authors

Ritu Bohat
Xiaofang Liang
Yanping Chen
Chunyu Xu
Ningbo Zheng
Ashley Guerrero
Jiakai Hou
Roshni Jaffery
Nicholas A Egan
Yaxi Li
Yitao Tang
Esra Unsal
Adolfo Robles
Si Chen
Angela M Major
Hadil Elldakli
Sang-Hyuk Chung
Han Liang
M John Hicks
Yong Du
Jamie S Lin
Xiqun Chen
Chandra Mohan
Weiyi Peng

Publication Date

1-1-2024

Journal

Journal of Clinical Immunology

DOI

10.1016/j.clim.2023.109874

PMID

38113962

PMCID

PMC12374782

PubMedCentral® Posted Date

8-25-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Sle1 and Fas^lpr are two lupus susceptibility loci that lead to manifestations of systemic lupus erythematosus. To evaluate the dosage effects of Fas^lpr in determining cellular and serological phenotypes associated with lupus, we developed a new C57BL/6 (B6) congenic lupus strain, B6.Sle1/Sle1.Fas^lpr/+ (Sle1homo.lprhet) and compared it with B6.Fas^lpr/lpr (lprhomo), B6.Sle1/Sle1 (Sle1homo), and B6.Sle1/Sle1.Fas^lpr/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 Fas^lpr were noted in upregulating serum IL-1α, 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.

Keywords

Mice, Animals, Mice, Inbred C57BL, Lupus Erythematosus, Systemic, Autoimmunity, Cell Differentiation, Gene Dosage, Mice, Inbred MRL lpr, Lupus, Genetics, FAS, Autoimmune Disease

Published Open-Access

yes

Recommended Citation

Bohat, Ritu; Liang, Xiaofang; Chen, Yanping; et al., "Faslpr Gene Dosage Tunes the Extent of Lymphoproliferation and T Cell Differentiation in Lupus" (2024). Faculty, Staff and Student Publications. 4736.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4736