한빛사논문
- 조회629
Carlos A. Castellanos1, Xin Ren2, Steven Lomeli Gonzalez1, Hong Kun Li1, Andrew W. Schroeder3, Hong-Erh Liang4, Brian J. Laidlaw5, Donglei Hu6, Angel C.Y. Mak6, Celeste Eng6, José R. Rodríguez-Santana7, Michael LeNoir8, Qi Yan9, Juan C. Celedón10, Esteban G. Burchard6,11, Scott S. Zamvil12, Satoshi Ishido13, Richard M. Locksley14, Jason G. Cyster15, Xiaozhu Huang2, Jeoung-Sook Shin1*
1Department of Microbiology and Immunology, Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA. 2Department of Medicine, Lung Biology Center, University of California, San Francisco, San Francisco, CA 94158, USA. 3Department of Pulmonology, Genomics CoLabs, University of California, San Francisco, San Francisco, CA 94158, USA. 4Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. 5Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA. 6Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA. 7Centro de Neumología Pediátrica, San Juan, Puerto Rico 00917, USA. 8Bay Area Pediatrics, Oakland, CA 94609, USA. 9Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, NY 10032, USA. 10Division of Pediatric Pulmonary Medicine, UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15224, USA. 11Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA. 12Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA. 13Department of Microbiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan. 14Department of Medicine, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA. 15Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
*Corresponding author.
Abstract
Type 2 T helper (TH2) cells are protective against parasitic worm infections but also aggravate allergic inflammation. Although the role of dendritic cells (DCs) in TH2 cell differentiation is well established, the underlying mechanisms are largely unknown. Here, we show that DC induction of TH2 cells depends on membrane-associated RING-CH-1 (MARCH1) ubiquitin ligase. The pro-TH2 effect of MARCH1 relied on lymph node (LN)–resident DCs, which triggered T cell receptor (TCR) signaling and induced GATA-3 expression from naïve CD4+ T cells independent of tissue-driven migratory DCs. Mice with mutations in the ubiquitin acceptor sites of MHCII and CD86, the two substrates of MARCH1, failed to develop TH2 cells. These findings suggest that TH2 cell development depends on ubiquitin-mediated clearance of antigen-presenting and costimulatory molecules by LN-resident DCs and consequent control of TCR signaling.
논문정보
- Research article
- 2021년 10월 (BRIC 등록일 2021-10-29)
- 국외 연구진
- 생명과학 > 면역학
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