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Int J Mol Sci. 2019 Sep 11;20(18). pii: E4505. doi: 10.3390/ijms20184505.

BTLA Expression on Th1, Th2 and Th17 Effector T-Cells of Patients with Systemic Lupus Erythematosus Is Associated with Active Disease.

Author information

1
Department of Nephrology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany. Christoph_Oster@web.de.
2
Department of Nephrology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany. Benjamin.Wilde@uk-essen.de.
3
Department of Rheumatology and Clinical Immunology, Kliniken Essen-Mitte, 45239 Essen, Germany. C.Specker@kem-med.com.
4
Department of Nephrology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany. ming.sun@stud.uni-due.de.
5
Department of Nephrology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany. Andreas.Kribben@uk-essen.de.
6
Department of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany. Oliver.Witzke@uk-essen.de.
7
Department of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany. Sebastian.Dolff@uk-essen.de.

Abstract

An imbalanced T-cell homeostasis plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). Co-stimulatory and co-inhibitory molecules regulate T-cell differentiation, survival, and cytokine production. B- and T-lymphocyte attenuator (BTLA) is a co-inhibitory molecule which negatively regulates T-cell activation. The aim of this study was to investigate BTLA expression on regulatory and effector CD4+ T-cells in SLE patients with and without lupus nephritis (LN) during active and inactive disease. Therefore, peripheral blood of forty-one SLE patients and twenty-one healthy controls (HC) was phenotypically analyzed. Next, ex vivo stimulated T-cells were analyzed for the expression of BTLA on Th1-, Th2-, and Th17-effector cells by flow cytometry. Renal involvement was defined as biopsy-proven LN. Disease activity was assessed by SLE disease activity index (SLEDAI). Percentages of peripheral unstimulated BTLA+ CD4+ T-cells were significantly decreased in SLE patients with active disease. However, ex vivo stimulated Th1, Th2, and Th17 effector T-cells, expressed increased percentages of BTLA expression in active disease. In contrast, the BTLA expression on CD4+CD25++CD127- regulatory T-cells was not significantly different. BTLA seems to be an important co-inhibitory molecule in the T-cell homeostasis of patients with systemic lupus erythematosus and crucial for disease activity.

KEYWORDS:

BTLA; Costimulation; IFN-γ; IL-10; IL-17A; SLE

PMID:
31514450
DOI:
10.3390/ijms20184505
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