IL-33 contributes to sepsis-induced long-term immunosuppression by expanding the regulatory T cell population

Abstract

Patients who survive sepsis can develop long-term immune dysfunction, with expansion of the regulatory T (Treg) cell population. However, how Treg cells proliferate in these patients is not clear. Here we show that IL-33 has a major function in the induction of this immunosuppression. Mice deficient in ST2 (IL-33R) develop attenuated immunosuppression in cases that survive sepsis, whereas treatment of naive wild-type mice with IL-33 induces immunosuppression. IL-33, released during tissue injury in sepsis, activates type 2 innate lymphoid cells, which promote polarization of M2 macrophages, thereby enhancing expansion of the Treg cell population via IL-10. Moreover, sepsis-surviving patients have more Treg cells, IL-33 and IL-10 in their peripheral blood. Our study suggests that targeting IL-33 may be an effective treatment for sepsis-induced immunosuppression.

Abstract

Patients who survive sepsis are at increased risk of infection owing to long-term immunosuppression that is associated with an increase in Treg cell numbers. Here the authors show expansion of the Treg cell population in sepsis mice is driven by IL-33-induced ILC2 activation of IL-10 production by macrophages.