Inhibition of glucose metabolism selectively targets autoreactive follicular helper T cells

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.