Inhibition of glucose metabolism selectively targets autoreactive follicular helper T cells

Abstract

Follicular helper T (T_FH) cells are expanded in systemic lupus erythematosus, where they are required to produce high affinity autoantibodies. Eliminating T_FH cells would, however compromise the production of protective antibodies against viral and bacterial pathogens. Here we show that inhibiting glucose metabolism results in a drastic reduction of the frequency and number of T_FH cells in lupus-prone mice. However, this inhibition has little effect on the production of T-cell-dependent antibodies following immunization with an exogenous antigen or on the frequency of virus-specific T_FH cells induced by infection with influenza. In contrast, glutaminolysis inhibition reduces both immunization-induced and autoimmune T_FH cells and humoral responses. Solute transporter gene signature suggests different glucose and amino acid fluxes between autoimmune T_FH cells and exogenous antigen-specific T_FH cells. Thus, blocking glucose metabolism may provide an effective therapeutic approach to treat systemic autoimmunity by eliminating autoreactive T_FH cells while preserving protective immunity against pathogens.