Group 2 innate lymphoid cells regulate nociceptive and gait functions of the peripheral nervous system

Deshpande D, Velleman L, Schmitz J, Forster PM, Schinke C, Boulekou S, Düsedau HP, Krug SM, Mertens T, Gao X, Figueiredo C, Jarick KJ, Plum T, Sterczyk N, Leclère PS, Helfrich S, Tappe-Theodor A, Kotsch K, Steffen J, Vöhringer D, Duerr CU, Hauser AE, Artis D, Pitzer C, Dunay IR, Klose CS (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Science immunology American Association for the Advancement of Science

Book Volume: 10

Pages Range: eadp7092-

Journal Issue: 111

DOI: 10.1126/sciimmunol.adp7092

Abstract

The peripheral nervous system (PNS) is involved in nociception and gait. The contribution of PNS-resident immune cells to these functions is not fully understood. We identified group 2 innate lymphoid cells (ILC2s) as a distinct immune cell population resident in the PNS, with a unique gene profile facilitating neuron-ILC2 cross-talk. ILC2-deficient mice display PNS dysfunction (hypersensitivity and gait anomalies). These functional deficits are attributed to structural abnormalities in the sciatic nerves of ILC2-deficient mice. ILC2s communicate with dorsal root ganglion neurons via the interleukin-13 (IL-13) signaling pathway to maintain nerve structure and pain thresholds. Loss of the shared IL-4/IL-13 receptor (IL-4R/IL-13R) in neurons results in a phenotype similar to ILC2-deficient mice. Intrathecally administered IL-13 rescues hypersensitivity and gait defects in ILC2-deficient mice, which suggests that this signaling pathway may be therapeutically important. This work therefore identifies a function for ILC2s in regulating the nerve structural integrity and nociceptive functions of the PNS.

Authors with CRIS profile

David Vöhringer Department of Infection Biology

Involved external institutions

Freie Universität Berlin DE Germany (DE) Otto-von-Guericke-Universität Magdeburg DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Ruprecht-Karls-Universität Heidelberg DE Germany (DE) Weill Cornell Medicine US United States (USA) (US)

How to cite

APA:

Deshpande, D., Velleman, L., Schmitz, J., Forster, P.M., Schinke, C., Boulekou, S.,... Klose, C.S. (2025). Group 2 innate lymphoid cells regulate nociceptive and gait functions of the peripheral nervous system. Science immunology, 10(111), eadp7092-. https://doi.org/10.1126/sciimmunol.adp7092

MLA:

Deshpande, Divija, et al. "Group 2 innate lymphoid cells regulate nociceptive and gait functions of the peripheral nervous system." Science immunology 10.111 (2025): eadp7092-.

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