Article
Pathophysiological relevance of B cell activating factor (BAFF) for autoimmunological and inflammatory organ destruction
Search Medline for
Authors
Published: | October 8, 2019 |
---|
Outline
Text
Background: The B cell activating factor (BAFF), a cytokine of the tumor necrosis factor (TNF) family, mainly produced by hematopoietic cells, plays an essential role in activation, differentiation and survival of B cells. There is considerable evidence that beside its function as an inflammatory cytokine BAFF also acts regulatory. BAFF levels in sera of SLE patients correlate with disease activity and are higher in some LN patients (only Type III and IV LN of ISN/RPS classification). Moreover, we could show that BAFF expression is not restricted to myeloid cells, even renal tubular epithelial cells (TEC) express BAFF. Thereby, BAFF expression levels of TEC correlate with disease activity in MRL/MpJ-Faslpr/J mice. However, precise systemic influence of BAFF in SLE needs to be further investigated.
Methods: The research objective of this study is a detailed analysis of the BAFF/BAFF receptor (BAFF-R) system with regard to different immunological and inflammatory kidney damages. For this purpose BAFF/BAFF-R knockout mice will be generated in the murine lupus model MRL/MpJ-Faslpr/J. In advance of generating and evaluating the BAFF/BAFF-R deficient murine lupus model kidney stress tests will be performed in vivo and thereby ischemic, mechanical and inflammatory stimuli of renal destruction tested in particular.
Results: These models will be analysed in the autoimmunological MRL/MpJ-Faslpr/J mouse strain and compared to kidney stress tests in autoimmunological not predestinated mouse strains as B6.129S2-Tnfsf13btmMsc/J and B6(Cg)-Tnfrsf13ctm1Mass/J. Furthermore, the impact of autoimmunological and inflammatory signal pathways will be observed in cell culture experiments.
Preliminary data on the differential effects of BAFF in autoimmunological versus autoinflammatory signal pathways will be shown.
Conclusion: The BAFF/BAFF-R system has bivalent effects on various autoimmune disorders and thereby acts protective as well as stimulating. This project investigates effect mechanisms dependent on different renal destruction stimuli and surrounding factors.