2. Academic Validation
  3. The protective roles of integrin α4β7 and Amphiregulin-expressing innate lymphoid cells in lupus nephritis

The protective roles of integrin α4β7 and Amphiregulin-expressing innate lymphoid cells in lupus nephritis

  • Cell Mol Immunol. 2024 Jul;21(7):723-737. doi: 10.1038/s41423-024-01178-2.
Seungwon Ryu 1,  Kyung Ah Kim 2,  Jinwoo Kim 3,  Dong Hun Lee 4 5 6,  Yong-Soo Bae 7 8,  Hajeong Lee 9,  Byoung Choul Kim 2,  Hye Young Kim 10 11 12
Affiliations

Affiliations

  • 1 Department of Microbiology, Gachon University College of Medicine, Incheon, 21999, South Korea.
  • 2 Department of Nano-Bioengineering, Incheon National University, Incheon, 22012, South Korea.
  • 3 Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, South Korea.
  • 4 Department of Dermatology, Seoul National University College of Medicine, Seoul, 03080, South Korea.
  • 5 Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, 03080, South Korea.
  • 6 Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, 03080, South Korea.
  • 7 Department of Biological Sciences, SRC Center for Immune Research on Non-lymphoid Organs, Sungkyunkwan University, Suwon, 16419, South Korea.
  • 8 Department of Biological Sciences, Sungkyunkwan University, Suwon, 16419, South Korea.
  • 9 Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, 03080, South Korea.
  • 10 Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, South Korea. hykim11@snu.ac.kr.
  • 11 Department of Biological Sciences, SRC Center for Immune Research on Non-lymphoid Organs, Sungkyunkwan University, Suwon, 16419, South Korea. hykim11@snu.ac.kr.
  • 12 Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul National University College of Medicine, Seoul, 03080, South Korea. hykim11@snu.ac.kr.
PMID: 38806623 DOI: 10.1038/s41423-024-01178-2
Abstract

Type 2 innate lymphoid cells (ILC2s) have emerged as key regulators of the immune response in renal inflammatory diseases such as lupus nephritis. However, the mechanisms underlying ILC2 adhesion and migration in the kidney remain poorly understood. Here, we revealed the critical role of Integrin α4β7 in mediating renal ILC2 adhesion and function. We found that Integrin α4β7 enables the retention of ILC2s in the kidney by binding to VCAM-1, E-cadherin, or fibronectin on structural cells. Moreover, Integrin α4β7 knockdown reduced the production of the reparative cytokine Amphiregulin (Areg) by ILC2s. In lupus nephritis, TLR7/9 signaling within the kidney microenvironment downregulates Integrin α4β7 expression, leading to decreased Areg production and promoting the egress of ILC2s. Notably, IL-33 treatment upregulated Integrin α4β7 and Areg expression in ILC2s, thereby enhancing survival and reducing inflammation in lupus nephritis. Together, these findings highlight the potential of targeting ILC2 adhesion as a therapeutic strategy for autoimmune kidney diseases.

Keywords

Adhesion molecules; Amphiregulin; Innate lymphoid cells; Integrins; Kidney; Lupus nephritis; Tissue residency.

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