Massachusetts Institute of Technology

The Brigham and Women's Hospital, Inc.

The Broad Institute, Inc.

Patrick R Burkett

Aviv Regev

Vijay K Kuchroo

Ana Carrizosa Anderson

Samantha J Riesenfeld

Monika S Kowalczyk

Antonia Wallrapp

Nicole Joller

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

Patrick R Burkett