| Autor: |
Man Lyang Kim, Melinda Y. Hardy, Laura E. Edgington-Mitchell, Sri H. Ramarathinam, Shan Zou Chung, Amy K. Russell, Iain Currie, Brad E. Sleebs, Anthony W. Purcell, Jason A. Tye-Din, Ian P. Wicks |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 24, Iss 12, Pp 103509- (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2021.103509 |
| Popis: |
Summary: Although hydroxychloroquine (HCQ) has long been used to treat autoimmune diseases, its mechanism of action remains poorly understood. In CD4 T-cells, we found that a clinically relevant concentration of HCQ inhibited the mitochondrial antioxidant system triggered by TCR crosslinking, leading to increased mitochondrial superoxide, impaired activation-induced autophagic flux, and reduced proliferation of CD4 T-cells. In antigen-presenting cells, HCQ also reduced constitutive activation of the endo-lysosomal protease legumain and toll-like receptor 9, thereby reducing cytokine production, but it had little apparent impact on constitutive antigen processing and peptide presentation. HCQ's effects did not require endo-lysosomal pH change, nor impaired autophagosome-lysosome fusion. We explored the clinical relevance of these findings in patients with celiac disease—a prototypic CD4 T-cell-mediated disease—and found that HCQ limits ex vivo antigen-specific T cell responses. We report a T-cell-intrinsic immunomodulatory effect from HCQ and suggest potential re-purposing of HCQ for celiac disease. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
