B-cell lymphoma 6 protein modulates function of human tonsillar innate lymphoid cells

Abstract

Abstract Innate lymphoid cells (ILC) play a fundamental role in mucosal homeostasis and immunity via expression of cytokines such as IL-22, IL-17A and IFN-γ. However, the transcriptional network that controls ILC functional identity is incompletely defined. Previously, we demonstrated that BCL6 plays a key role in transcriptional regulation in mouse intestinal ILC1 and ILC3. Here, we performed in vitro cultures of ILCs isolated from human tonsil in the presence of cytokines that promote ILC1 or ILC3 in order to assess the role of BCL6 in functional plasticity of ILCs. ILCs were treated with IL-2 and IL-12/IL-1β or IL-23/IL-1β in the presence or absence of the BCL6 inhibitor FX-1. In the context of IL-12/IL-1β ILC1-promoting culture, FX-1 inhibition of BCL6 reduced expression of Tbet and IFN-γ. In contrast, BCL6 inhibition in the context of IL-23/IL-1β ILC3-inducing conditions had no effect on Tbet, IFN-γ, or RORγt. In either context, FX-1 resulted in reduced IL-22 but increased IL-17A expression in comparison to vehicle treated cultures. Thus, our data emphasizes the role of BCL6 as a regulator of human tonsil ILC functional identity.