김혜영 (서울대학교 의과대학) | 한빛사논문 > 한빛사

한빛사논문

조회368

서울대학교 의과대학

CV File 125 kb

Cell. Mol. Immunol., May 28 2024, | https://doi.org/10.1038/s41423-024-01178-2 The protective roles of integrin α4β7 and Amphiregulin-expressing innate lymphoid cells in lupus nephritis

Seungwon Ryu¹, Kyung Ah Kim², Jinwoo Kim³, Dong Hun Lee^4,5,6, Yong-Soo Bae^7,8, Hajeong Lee⁹, Byoung Choul Kim² and Hye Young Kim^3,7,10

¹Department of Microbiology, Gachon University College of Medicine, Incheon 21999, South Korea.

²Department of Nano-Bioengineering, Incheon National University, Incheon 22012, South Korea.

³Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea.

⁴Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, South Korea.

⁵Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, South Korea.

⁶Institute of Human–Environment Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, South Korea.

⁷Department of Biological Sciences, SRC Center for Immune Research on Non-lymphoid Organs, Sungkyunkwan University, Suwon 16419, South Korea.

⁸Department of Biological Sciences, Sungkyunkwan University, Suwon 16419, South Korea.

⁹Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital and Seoul National University College of Medicine, Seoul 03080, South Korea.

¹⁰Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul National University College of Medicine, Seoul 03080, South Korea.

Corresponding author

Correspondence to Hye Young Kim.

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.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-05-29)
연구진국내 연구진
분야 의약학 > 면역의학

댓글 작성 로그인

CV 열람하기

연락처 보기