Massachusetts Institute of Technology

The Brigham and Women's Hospital, Inc.

The Broad Institute, Inc.

Antonia Wallrapp

Aviv Regev

Vijay K Kuchroo

Samantha J Riesenfeld

Monika S Kowalczyk

Patrick R Burkett

Computational and functional analysis identified the neuropeptide receptor Nmur1 as selectively expressed on Type 2 innate lymphoid cells (ILC2s). While both IL-33 and IL-25 promote ILC activation in vivo, IL-33 induces robust ILC proliferation, whereas ILCs activated with IL-25 do not proliferate as robustly and up-regulate Nmur1 expression. Treatment with neuromedin U (NMU), the neuropeptide ligand of Nmur1, had little effect on its own. Co-administration of IL-25 with NMU, however, dramatically amplified allergic lung inflammation and induced the proliferation and expansion of specific ILC2 subsets, characterized by a molecular signature unique to pro-inflammatory ILC2s. The results demonstrate that Nmur1 signaling strongly modulates IL-25-mediated ILC2 responses, resulting in highly proliferative pro-inflammatory ILCs, and highlights the importance of neuro-immune crosstalk in allergic inflammatory responses at mucosal surfaces.

Methods and compositions for regulating innate lymphoid cell inflammatory responses

Growing community of inventors

Boston, MA, United States of America

Antonia Wallrapp