IL-6 activated integrated BATF/IRF4 functions in lymphocytes are T-bet-independent and reversed by subcutaneous immunotherapy

IL-6 plays a central role in supporting pathological T(H2) and T(H17) cell development and inhibiting the protective T regulatory cells in allergic asthma. T(H17) cells have been demonstrated to regulate allergic asthma in general and T-bet-deficiency-induced asthma in particular. Here we found an inverse correlation between T-bet and Il-6 mRNA expression in asthmatic children. Moreover, experimental subcutaneous immunotherapy (SIT) in T-bet((−/−)) mice inhibited IL-6, IL-21R and lung T(H17) cells in a setting of asthma. Finally, local delivery of an anti-IL-6R antibody in T-bet((−/−)) mice resulted in the resolution of this allergic trait. Noteworthy, BATF, crucial for the immunoglobulin-class-switch and T(H2),T(H17) development, was found down-regulated in the lungs of T-bet((−/−)) mice after SIT and after treatment with anti-IL-6R antibody, indicating a critical role of IL-6 in controlling BATF/IRF4 integrated functions in T(H2), T(H17) cells and B cells also in a T-bet independent fashion in allergic asthma.