Hong Kong Guangdong Rheumatology Meeting

Abstract

Metabolic reprograming drives the activation of lymphocytes, allowing them to turn into highly autoreactive T cells and B cells in systemic lupus erythematosus (SLE). Metabolic demands among immune cell types are distinct and metabolic reprograming is associated with immune cell development, activation and differentiation. Recent advances in immunometabolism has defined T/B cell behaviors by the intricate interplay between metabolic rewriting and T/B cell functions. During T cell activation, T cells rely on glucose glycolysis for bioenergy fulfillment. While B cells, germinal center B cells in particular, tend to consume fatty acid for ATP synthesis. Our data revealed that T cells from patients with lupus nephritis (LN) exhibit higher level of glycose glycolysis. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the salvage NAD+ biosynthetic pathway cntrol IFN[Formula: see text] production by CD4+ T cells in LN. Inhibition of NAMPT suppressed IFN[Formula: see text] production in CD4+ T cells and reduced inflammatory infiltrates in lupus mice. In addition, CD36-mediated lipid uptake is enhanced in SLE B cells. Accordingly, the inhibition of fatty acid oxidation results in reduced autoreactive B cell responses and ameliorated diseases in lupus mice. Ablation of CD36 in B cells impairs lipid uptake and differentiation of autoreactive B cells during autoimmune induction. Targeting the metabolic pathways that regulate T/B cell activation could modulate the metabolic reprogramming of these lymphocytes, which could have important indications for the therapy of patients with LN.