IL7RA single nucleotide polymorphisms are associated with the size and function of the MAIT cell population in treated HIV-1 infection
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 poly...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-10-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.985385/full |
| _version_ | 1811251136314736640 |
|---|---|
| author | Fei Han Fei Han Muhammad Yaaseen Gulam Yichao Zheng Yichao Zheng Nurul Syuhada Zulhaimi Nurul Syuhada Zulhaimi Wan Rong Sia Dan He Dan He Amanda Ho Amanda Ho Leila Hadadi Zhenyu Liu Zhenyu Liu Peiwu Qin Peiwu Qin Peter E. Lobie Peter E. Lobie Adeeba Kamarulzaman Adeeba Kamarulzaman Lin-Fa Wang Johan K. Sandberg Sharon R. Lewin Reena Rajasuriar Reena Rajasuriar Reena Rajasuriar Edwin Leeansyah Edwin Leeansyah Edwin Leeansyah Edwin Leeansyah |
| author_facet | Fei Han Fei Han Muhammad Yaaseen Gulam Yichao Zheng Yichao Zheng Nurul Syuhada Zulhaimi Nurul Syuhada Zulhaimi Wan Rong Sia Dan He Dan He Amanda Ho Amanda Ho Leila Hadadi Zhenyu Liu Zhenyu Liu Peiwu Qin Peiwu Qin Peter E. Lobie Peter E. Lobie Adeeba Kamarulzaman Adeeba Kamarulzaman Lin-Fa Wang Johan K. Sandberg Sharon R. Lewin Reena Rajasuriar Reena Rajasuriar Reena Rajasuriar Edwin Leeansyah Edwin Leeansyah Edwin Leeansyah Edwin Leeansyah |
| author_sort | Fei Han |
| collection | DOAJ |
| description | 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-7Rα (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-7Rα 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-7Rα in vitro suppressed IL-7-dependent MAIT cell proliferation and function following cognate stimulations. These observations suggest that sIL-7Rα 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. |
| first_indexed | 2024-04-12T16:15:07Z |
| format | Article |
| id | doaj.art-fe0e1e3212784ad38a988241e4ae7f80 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T16:15:07Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-fe0e1e3212784ad38a988241e4ae7f802022-12-22T03:25:45ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.985385985385IL7RA single nucleotide polymorphisms are associated with the size and function of the MAIT cell population in treated HIV-1 infectionFei Han0Fei Han1Muhammad Yaaseen Gulam2Yichao Zheng3Yichao Zheng4Nurul Syuhada Zulhaimi5Nurul Syuhada Zulhaimi6Wan Rong Sia7Dan He8Dan He9Amanda Ho10Amanda Ho11Leila Hadadi12Zhenyu Liu13Zhenyu Liu14Peiwu Qin15Peiwu Qin16Peter E. Lobie17Peter E. Lobie18Adeeba Kamarulzaman19Adeeba Kamarulzaman20Lin-Fa Wang21Johan K. Sandberg22Sharon R. Lewin23Reena Rajasuriar24Reena Rajasuriar25Reena Rajasuriar26Edwin Leeansyah27Edwin Leeansyah28Edwin Leeansyah29Edwin Leeansyah30Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, ChinaPrecision Medicine and Healthcare Research Centre, Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, ChinaProgramme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, SingaporeInstitute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, ChinaPrecision Medicine and Healthcare Research Centre, Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, ChinaCentre of Excellence for Research in AIDS (CERiA), University of Malaya, Kuala Lumpur, MalaysiaDepartment of Medicine, University of Malaya, Kuala Lumpur, MalaysiaProgramme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, SingaporeInstitute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, ChinaPrecision Medicine and Healthcare Research Centre, Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, ChinaInstitute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, ChinaPrecision Medicine and Healthcare Research Centre, Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, ChinaProgramme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, SingaporeInstitute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, ChinaPrecision Medicine and Healthcare Research Centre, Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, ChinaInstitute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, ChinaPrecision Medicine and Healthcare Research Centre, Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, ChinaInstitute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, ChinaPrecision Medicine and Healthcare Research Centre, Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, ChinaCentre of Excellence for Research in AIDS (CERiA), University of Malaya, Kuala Lumpur, MalaysiaDepartment of Medicine, University of Malaya, Kuala Lumpur, MalaysiaProgramme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, SingaporeCenter for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, SwedenPeter Doherty Institute for Infection and Immunity, Melbourne University, Victoria, AustraliaCentre of Excellence for Research in AIDS (CERiA), University of Malaya, Kuala Lumpur, MalaysiaDepartment of Medicine, University of Malaya, Kuala Lumpur, MalaysiaPeter Doherty Institute for Infection and Immunity, Melbourne University, Victoria, AustraliaInstitute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, ChinaPrecision Medicine and Healthcare Research Centre, Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, ChinaProgramme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, SingaporeCenter for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, SwedenMAIT 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-7Rα (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-7Rα 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-7Rα in vitro suppressed IL-7-dependent MAIT cell proliferation and function following cognate stimulations. These observations suggest that sIL-7Rα 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.985385/fullMAIT cellsHIV-1IL-7CD127 (IL7Ra) geneantiretroviral (ARV) therapy |
| spellingShingle | Fei Han Fei Han Muhammad Yaaseen Gulam Yichao Zheng Yichao Zheng Nurul Syuhada Zulhaimi Nurul Syuhada Zulhaimi Wan Rong Sia Dan He Dan He Amanda Ho Amanda Ho Leila Hadadi Zhenyu Liu Zhenyu Liu Peiwu Qin Peiwu Qin Peter E. Lobie Peter E. Lobie Adeeba Kamarulzaman Adeeba Kamarulzaman Lin-Fa Wang Johan K. Sandberg Sharon R. Lewin Reena Rajasuriar Reena Rajasuriar Reena Rajasuriar Edwin Leeansyah Edwin Leeansyah Edwin Leeansyah Edwin Leeansyah IL7RA single nucleotide polymorphisms are associated with the size and function of the MAIT cell population in treated HIV-1 infection Frontiers in Immunology MAIT cells HIV-1 IL-7 CD127 (IL7Ra) gene antiretroviral (ARV) therapy |
| title | IL7RA single nucleotide polymorphisms are associated with the size and function of the MAIT cell population in treated HIV-1 infection |
| title_full | IL7RA single nucleotide polymorphisms are associated with the size and function of the MAIT cell population in treated HIV-1 infection |
| title_fullStr | IL7RA single nucleotide polymorphisms are associated with the size and function of the MAIT cell population in treated HIV-1 infection |
| title_full_unstemmed | IL7RA single nucleotide polymorphisms are associated with the size and function of the MAIT cell population in treated HIV-1 infection |
| title_short | IL7RA single nucleotide polymorphisms are associated with the size and function of the MAIT cell population in treated HIV-1 infection |
| title_sort | il7ra single nucleotide polymorphisms are associated with the size and function of the mait cell population in treated hiv 1 infection |
| topic | MAIT cells HIV-1 IL-7 CD127 (IL7Ra) gene antiretroviral (ARV) therapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.985385/full |
| work_keys_str_mv | AT feihan il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT feihan il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT muhammadyaaseengulam il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT yichaozheng il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT yichaozheng il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT nurulsyuhadazulhaimi il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT nurulsyuhadazulhaimi il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT wanrongsia il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT danhe il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT danhe il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT amandaho il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT amandaho il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT leilahadadi il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT zhenyuliu il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT zhenyuliu il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT peiwuqin il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT peiwuqin il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT peterelobie il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT peterelobie il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT adeebakamarulzaman il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT adeebakamarulzaman il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT linfawang il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT johanksandberg il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT sharonrlewin il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT reenarajasuriar il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT reenarajasuriar il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT reenarajasuriar il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT edwinleeansyah il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT edwinleeansyah il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT edwinleeansyah il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection AT edwinleeansyah il7rasinglenucleotidepolymorphismsareassociatedwiththesizeandfunctionofthemaitcellpopulationintreatedhiv1infection |