ALLOSTERIC CD11b INTEGRIN ACTIVATION SUPPRESSES TLR7 SIGNALING PATHWAY IN LUPUS NEPHRITIS

Abstract

Lupus nephritis (LN) affects more than one-third of all systemic lupus erythematosus (SLE) patients and associated with increased risk of patient death. Myeloid cell, macrophage, and neutrophil influxes that occur in LN cause glomerulonephritis and severe inflammation, which in turn cause significant kidney damage. Strong correlations have been found between SLE and the integrin alpha M (ITGAM) gene. CD11b, the α-chain of the integrin receptor CD11b/CD18, encoded by ITGAM. The majority of innate immune cells include the CD11b/CD18 integrin, which is connected to cell migration, adhesion, and signaling. Previous research has shown that integrin activation can decrease the inflammatory response by linking integrin conformation to IFN-1 and NF-B signaling. In this thesis, we investigate two aims. Firstly, to further investigate the changes in TLR7-dependent pro-inflammatory pathways upon CD11b activation using macrophages cell line. Second, examine the cytokines and signaling pathways that are influenced by CD11b activation in primary cells. Strong links have been found in this study imply that CD11b activation decreases inflammation and suggests that CD11b activation is effective as a therapy for SLE and more particularly LN.