2. Academic Validation
  3. SLAM-family receptors promote resolution of ILC2-mediated inflammation

SLAM-family receptors promote resolution of ILC2-mediated inflammation

  • Nat Commun. 2024 Jun 13;15(1):5056. doi: 10.1038/s41467-024-49466-9.
Yuande Wang 1 2,  Yuhe Quan 2,  Junming He 2,  Shasha Chen 3 4 5 6,  Zhongjun Dong 7 8 9 10 11
Affiliations

Affiliations

  • 1 Department of Allergy, the First Affiliated Hospital of Anhui Medical University and Institute of Clinical Immunology, Anhui Medical University, Hefei, 230032, China.
  • 2 State Key Laboratory of Membrane Biology, School of Medicine and Institute for Immunology, Tsinghua University, Beijing, 100084, China.
  • 3 Department of Allergy, the First Affiliated Hospital of Anhui Medical University and Institute of Clinical Immunology, Anhui Medical University, Hefei, 230032, China. chenshasha.26@163.com.
  • 4 Innovative Institute of Tumor Immunity and Medicine (ITIM), Hefei, 230032, China. chenshasha.26@163.com.
  • 5 Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy, Hefei, 230032, China. chenshasha.26@163.com.
  • 6 Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, 230032, China. chenshasha.26@163.com.
  • 7 Department of Allergy, the First Affiliated Hospital of Anhui Medical University and Institute of Clinical Immunology, Anhui Medical University, Hefei, 230032, China. dongzj@mail.tsinghua.edu.cn.
  • 8 State Key Laboratory of Membrane Biology, School of Medicine and Institute for Immunology, Tsinghua University, Beijing, 100084, China. dongzj@mail.tsinghua.edu.cn.
  • 9 Innovative Institute of Tumor Immunity and Medicine (ITIM), Hefei, 230032, China. dongzj@mail.tsinghua.edu.cn.
  • 10 Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy, Hefei, 230032, China. dongzj@mail.tsinghua.edu.cn.
  • 11 Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, 230032, China. dongzj@mail.tsinghua.edu.cn.
PMID: 38871792 DOI: 10.1038/s41467-024-49466-9
Abstract

Type 2 innate lymphoid cells (ILC2) initiate early allergic inflammation in the lung, but the factors that promote subsequent resolution of type 2 inflammation and prevent prolonged ILC2 activation are not fully known. Here we show that SLAM-family receptors (SFR) play essential roles in this process. We demonstrate dynamic expression of several SFRs on ILC2s during papain-induced type 2 immunity in mice. SFR deficiency exacerbates ILC2-driven eosinophil infiltration in the lung, and results in a significant increase in IL-13 production by ILC2s exclusively in mediastinal lymph nodes (MLN), leading to increased dendritic cell (DC) and TH2 cell numbers. In MLNs, we observe more frequent interaction between ILC2s and bystander T cells, with T cell-expressed SFRs (especially SLAMF3 and SLAMF5) acting as self-ligands to suppress IL-13 production by ILC2s. Mechanistically, homotypic engagement of SFRs at the interface between ILC2s and T cells delivers inhibitory signaling primarily mediated by SHIP-1. This prevents activation of NF-κB, driven by IL-7 and IL-33, two major drivers of ILC2-mediated type 2 immunity. Thus, our study shows that an ILC2-DC-TH2 regulatory axis may promote the resolution of pulmonary type 2 immune responses, and highlights SLAMF3/SLAMF5 as potential therapeutic targets for ameliorating type 2 immunity.

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