Group 2 innate lymphoid cells regulate nociceptive and gait functions of the peripheral nervous system
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
- Ildikò Rita Dunay (ORCID: https://orcid.org/0000-0002-9900-8605)
- David Artis (ORCID: https://orcid.org/0000-0002-1753-4100)
- Christian Schinke (ORCID: https://orcid.org/0000-0003-0199-9672)
- Sotiria Boulekou (ORCID: https://orcid.org/0000-0001-5520-4164)
- Johannes Steffen (ORCID: https://orcid.org/0000-0002-0647-4157)
- Christoph S. N. Klose (ORCID: https://orcid.org/0000-0001-8803-2979)
- Divija Deshpande (ORCID: https://orcid.org/0000-0001-9166-2509)
- Xuemei Gao (ORCID: https://orcid.org/0000-0002-2949-3609)
- Claudia U. Duerr (ORCID: https://orcid.org/0000-0002-5010-3994)
- Susanne M. Krug (ORCID: https://orcid.org/0000-0002-1293-2484)
- Sofia Helfrich (ORCID: https://orcid.org/0000-0002-9087-2958)
- David Voehringer (ORCID: https://orcid.org/0000-0001-6650-0639)
- Thomas Plum (ORCID: https://orcid.org/0000-0002-7811-4476)
- Henning Peter Düsedau (ORCID: https://orcid.org/0000-0002-0805-4084)
- Claudia Pitzer (ORCID: https://orcid.org/0000-0002-7663-1031)
- Janna Schmitz
- Anja E. Hauser (ORCID: https://orcid.org/0000-0002-7725-9526)
- Katja Kotsch (ORCID: https://orcid.org/0000-0002-3803-0964)
- Katja J. Jarick (ORCID: https://orcid.org/0000-0001-5162-7266)
- Caio Andreeta Figueiredo (ORCID: https://orcid.org/0000-0003-1517-5957)
- T. Mertens (ORCID: https://orcid.org/0009-0007-5605-6352)
- Pierre S. Leclère (ORCID: https://orcid.org/0000-0002-1794-9461)
- Anke Tappe‐Theodor (ORCID: https://orcid.org/0000-0002-9343-7580)
- Nele Sterczyk (ORCID: https://orcid.org/0009-0002-9052-1135)
- Patrycja M. Forster
- Laura Velleman (ORCID: https://orcid.org/0009-0002-7347-8067)
Institutions
- German Cancer Research Center (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Cornell University (US)
- Heidelberg University (DE)
- Leibniz Association (DE)
- Humboldt-Universität zu Berlin (DE)
- Universitätsklinikum Erlangen (DE)
- German Rheumatism Research Centre (DE)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- Charité - Universitätsmedizin Berlin (DE)
- Otto-von-Guericke-Universität Magdeburg (DE)
Publication Details
- Journal
- Science Immunology
- Published
- 2025-09-26
- DOI
- https://doi.org/10.1126/sciimmunol.adp7092
- Citations
- 4
- Primary Topic
- IL-33, ST2, and ILC Pathways
- Type
- article
- Field-Weighted Citation Impact
- 3.19