MARCH1 Controls an Exhaustion-like Program of Effector CD4 + T Cells Promoting Allergic Airway Inflammation.
| Autor: | Castellanos CA; Department of Microbiology and Immunology, Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA; carlos.castellanos@crick.ac.uk., Hiam-Galvez KJ; Department of Pathology, Stanford University School of Medicine, Stanford, CA; and., Ishido S; Department of Microbiology, Hyogo College of Medicine, Nishinomiya, Japan., Satpathy AT; Department of Pathology, Stanford University School of Medicine, Stanford, CA; and., Shin JS; Department of Microbiology and Immunology, Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | ImmunoHorizons [Immunohorizons] 2022 Sep 13; Vol. 6 (9), pp. 684-692. Date of Electronic Publication: 2022 Sep 13. |
| DOI: | 10.4049/immunohorizons.2200056 |
| Abstrakt: | Persistent antigenic signaling leads to T cell exhaustion, a dysfunctional state arising in many chronic infections and cancers. Little is known concerning mechanisms limiting exhaustion in immune-stimulatory diseases such as asthma. We report that membrane-associated RING-CH1 (MARCH1), the ubiquitin ligase that mediates surface turnover of MHC class II (MHCII) and CD86 in professional APCs, plays an essential role in restraining an exhaustion-like program of effector CD4 + T cells in a mouse model of asthma. Mice lacking MARCH1 or the ubiquitin acceptor sites of MHCII and CD86 exhibited increased MHCII and CD86 surface expression on lung APCs, and this increase promoted enhanced expression of immune-inhibitory receptors by effector CD4 + T cells and inhibited their proliferation. Remarkably, ablation of MARCH1 in mice with established asthma reduced airway infiltration of eosinophils and Th2 cells. Thus, MARCH1 controls an exhaustion-like program of effector CD4 + T cells during allergic airway inflammation and may serve as a therapeutic target for asthma. (Copyright © 2022 The Authors.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|