박은총 (Duke University, 현 AstraZeneca)

한빛사논문

조회713

박은총Eunchong Park

Duke University, 현 AstraZeneca

CV File 209 kb

Sci. Immunol., Oct 20 2023, 8 (88) | https://doi.org/10.1126/sciimmunol.adg7597 Integrin α3 promotes TH17 cell polarization and extravasation during autoimmune neuroinflammation.

Eunchong Park ^1,2, William E Barclay ¹, Alejandro Barrera ^2,3, Tzu-Chieh Liao ^1,2, Harmony R Salzler ¹, Timothy E Reddy ^2,3, Mari L Shinohara ^1,4, Maria Ciofani ^1,2,4*

¹Department of Integrative Immunobiology, Duke University Medical Center, Durham, NC, USA.

²Center for Advanced Genomic Technologies, Duke University, Durham, NC, USA.

³Department of Biostatistics and Bioinformatics, Duke University Medical School, Durham, NC, USA.

⁴Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA.

^*Corresponding author : Maria Ciofani

Abstract

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) caused by CNS-infiltrating leukocytes, including T _H17 cells that are critical mediators of disease pathogenesis. Although targeting leukocyte trafficking is effective in treating autoimmunity, there are currently no therapeutic interventions that specifically block encephalitogenic T _H17 cell migration. Here, we report integrin α3 as a T _H17 cell-selective determinant of pathogenicity in experimental autoimmune encephalomyelitis. CNS-infiltrating T _H17 cells express high integrin α3, and its deletion in CD4 ⁺ T cells or Il17a fate-mapped cells attenuated disease severity. Mechanistically, integrin α3 enhanced the immunological synapse formation to promote the polarization and proliferation of T _H17 cells. Moreover, the transmigration of T _H17 cells into the CNS was dependent on integrin α3, and integrin α3 deficiency enhanced the retention of CD4 ⁺ T cells in the perivascular space of the blood-brain barrier. Integrin α3-dependent interactions continuously maintain T _H17 cell identity and effector function. The requirement of integrin α3 in T _H17 cell pathogenicity suggests integrin α3 as a therapeutic target for MS treatment.

논문정보

형식Research article
게재일2023년 10월 (BRIC 등록일 2023-10-16)
연구진국외 연구진
분야 생명과학 > 면역학

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