Earticle

초록

영어

Complements, such as C1q and C3, and macrophages in the splenic marginal zone (MZMs) play pivotal roles in the efficient uptake and processing of circulating apoptotic cells. SIGN-R1, a C-type lectin that is highly expressed in a subpopulation of MZMs, regulates the complement fixation pathway by interacting with C1q, to fight blood-borne Streptococcus pneumoniae. Therefore, we examined whether the SIGN-R1-mediated classical complement pathway plays a role in apoptotic cell clearance and immune tolerance. SIGN-R1 first-bound apoptotic cells and this binding was significantly enhanced in the presence of C1q. SIGN-R1-C1q complex then immediately mediated C3 deposition on circulating apoptotic cells in the MZ, leading to the efficient clearance of them. SIGN-R1-mediated C3 deposition was completely abolished in the spleen of SIGN-R1 knockout (KO) mice. Given that SIGN-R1 is not expressed in the liver, we were struck by the finding that C3-deposited apoptotic cells were still found in the liver of wild-type mice, and dramatically reduced in the SIGN-R1 KO liver. In particular, SIGN-R1 deficiency caused delayed clearance of apoptotic cells and aberrant secretion of cytokines, such as TNF-α, IL-6, and TGF-β in the spleen as well as in the liver. In addition, anti-double- and single-stranded DNA antibody level was significantly increased in SIGN-R1-depleted mice compared with control mice. These findings suggest a novel mechanism of apoptotic cell clearance which is initiated by SIGN-R1 in the MZ and identify an integrated role of SIGN-R1 in the systemic clearance of apoptotic cells, linking the recognition of apoptotic cells, the opsonization of complements, and the induction of immune tolerance.

저자

• MG Prabagar [ Department of Biomedical Science and Technology, SMART Institute of Advanced Biomedical Science, Institute of Functional Genomics, Konkuk University ]
• Y Do [ Department of Biomedical Science and Technology, SMART Institute of Advanced Biomedical Science, Institute of Functional Genomics, Konkuk University ]
• S Ryu [ Department of Biomedical Science and Technology, SMART Institute of Advanced Biomedical Science, Institute of Functional Genomics, Konkuk University ]
• J-Y Park [ Department of Biomedical Science and Technology, SMART Institute of Advanced Biomedical Science, Institute of Functional Genomics, Konkuk University ]
• H-J Choi [ Department of Biomedical Science and Technology, SMART Institute of Advanced Biomedical Science, Institute of Functional Genomics, Konkuk University ]
• W-S Choi [ Department of Biomedical Science and Technology, SMART Institute of Advanced Biomedical Science, Institute of Functional Genomics, Konkuk University ]
• TJ Yun [ Department of Biomedical Science and Technology, SMART Institute of Advanced Biomedical Science, Institute of Functional Genomics, Konkuk University ]
• J Moon [ Department of Biomedical Science and Technology, SMART Institute of Advanced Biomedical Science, Institute of Functional Genomics, Konkuk University ]
• I-S Choi [ Department of Biomedical Science and Technology, SMART Institute of Advanced Biomedical Science, Institute of Functional Genomics, Konkuk University ]
• K Ko [ Department of Biomedical Science and Technology, SMART Institute of Advanced Biomedical Science, Institute of Functional Genomics, Konkuk University ]
• K Ko [ Department of Biomedical Science and Technology, SMART Institute of Advanced Biomedical Science, Institute of Functional Genomics, Konkuk University ]
• C Young Shin [ Department of Biomedical Science and Technology, SMART Institute of Advanced Biomedical Science, Institute of Functional Genomics, Konkuk University ]
• C Cheong [ Department of Biomedical Science and Technology, SMART Institute of Advanced Biomedical Science, Institute of Functional Genomics, Konkuk University ]
• Y-S Kang [ Department of Biomedical Science and Technology, SMART Institute of Advanced Biomedical Science, Institute of Functional Genomics, Konkuk University ]

참고문헌

발행기관

간행물

표지보기 관심저널 등록

• 간행물명

  한국당과학회 학술대회

• 간기

  연간

• 수록기간

  2006~2022

• 십진분류

  KDC 517 DDC 614