Massachusetts Institute of Technology

The Broad Institute, Inc.

The Brigham and Women's Hospital, Inc.

Yale University

Monika S Kowalczyk

Aviv Regev

Samantha J Riesenfeld

Richard A Flavell

Vijay K Kuchroo

Jan-Christian Huetter

Patrick R Burkett

Elena Torlai Triglia

Antonia Wallrapp

Piotr Bielecki

The subject matter disclosed herein is generally directed to methods and compositions for modulating inflammation driven by differentiation of quiescent tissue-resident ILCs into a spectrum of pathogenic effectors. The subject matter disclosed herein is also generally directed to detecting and monitoring an ILC response. Additionally, the subject matter is directed to treating skin inflammation, such as psoriasis.

Methods and compositions for modulating innate lymphoid cell pathogenic effectors

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

Cambridge, MA, United States of America

Monika S Kowalczyk