Han, Fei and Gulam, Muhammad Yaaseen and Zheng, Yichao and Zulhaimi, Nurul Syuhada and Sia, Wan Rong and He, Dan and Ho, Amanda and Hadadi, Leila and Liu, Zhenyu and Qin, Peiwu and Lobie, Peter E. and Kamarulzaman, Adeeba and Wang, Lin-Fa and Sandberg, Johan K. and Lewin, Sharon R. and Rajasuriar, Reena and Leeansyah, Edwin (2022) IL7RA single nucleotide polymorphisms are associated with the size and function of the MAIT cell population in treated HIV-1 infection. Frontiers in Immunology, 13. ISSN 1664-3224, DOI https://doi.org/10.3389/fimmu.2022.985385.
Full text not available from this repository.Abstract
MAIT cells are persistently depleted and functionally exhausted in HIV-1-infected patients despite long-term combination antiretroviral therapy (cART). IL-7 treatment supports MAIT cell reconstitution in vivo HIV-1-infected individuals and rescues their functionality in vitro. Single-nucleotide polymorphisms (SNPs) of the IL-7RA gene modulate the levels of soluble(s)IL-7R alpha (sCD127) levels and influence bioavailability of circulating IL-7. Here we evaluate the potential influence of IL-7RA polymorphisms on MAIT cell numbers and function in healthy control (HC) subjects and HIV-1-infected individuals on long-term cART. Our findings indicate that IL-7RA haplotype 2 (H2*T), defined as T-allele carriers at the tagging SNP rs6897932, affects the size of the peripheral blood MAIT cell pool, as well as their production of cytokines and cytolytic effector proteins in response to bacterial stimulation. H2*T carriers had lower sIL-7R alpha levels and higher MAIT cell frequency with enhanced functionality linked to higher expression of MAIT cell-associated transcription factors. Despite an average of 7 years on suppressive cART, MAIT cell levels and function in HIV-1-infected individuals were still significantly lower than those of HC. Notably, we observed a significant correlation between MAIT cell levels and cART duration only in HIV-1-infected individuals carrying IL-7RA haplotype 2. Interestingly, treatment with sIL-7R alpha in vitro suppressed IL-7-dependent MAIT cell proliferation and function following cognate stimulations. These observations suggest that sIL-7R alpha levels may influence MAIT cell numbers and function in vivo by limiting IL-7 bioavailability to MAIT cells. Collectively, these observations suggest that IL-7RA polymorphisms may play a significant role in MAIT cell biology and influence MAIT cells recovery in HIV-1 infection. The potential links between IL7RA polymorphisms, MAIT cell immunobiology, and HIV-1 infection warrant further studies going forward.
| Item Type: | Article |
|---|---|
| Funders: | Swedish Research Council 2015-00174, Jonas Soederquist Foundation for Virology and Immunology, Petrus and Augusta Hedlund Foundation, Tsinghua Shenzhen International Graduate School Research Startup Funds 01030100004, Shenzhen Pengcheng Peacock Program, High Impact Research grant (HIR/MOHE) H-20001-E000001, Marie Curie Actions INCA 600398 |
| Uncontrolled Keywords: | MAIT cells; HIV-1; IL-7; CD127 (IL7Ra) gene; Antiretroviral (ARV) therapy |
| Subjects: | Q Science > QR Microbiology > QR180 Immunology |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 04 Nov 2025 12:37 |
| Last Modified: | 04 Nov 2025 12:37 |
| URI: | http://eprints.um.edu.my/id/eprint/40787 |
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