TY - JOUR
T1 - IL7RA single nucleotide polymorphisms are associated with the size and function of the MAIT cell population in treated HIV-1 infection
AU - Han, Fei
AU - Gulam, Muhammad Yaaseen
AU - Zheng, Yichao
AU - Zulhaimi, Nurul Syuhada
AU - Sia, Wan Rong
AU - He, Dan
AU - Ho, Amanda
AU - Hadadi, Leila
AU - Liu, Zhenyu
AU - Qin, Peiwu
AU - Lobie, Peter E.
AU - Kamarulzaman, Adeeba
AU - Wang, Lin Fa
AU - Sandberg, Johan K.
AU - Lewin, Sharon R.
AU - Rajasuriar, Reena
AU - Leeansyah, Edwin
N1 - Funding Information:
The research was supported by grants from Swedish Research Council Grant 2015-00174, Marie Skłodowska Curie Actions, Cofund, Project INCA 600398, the Jonas Söderquist Foundation for Virology and Immunology, the Petrus and Augusta Hedlund Foundation, Tsinghua Shenzhen International Graduate School Research Startup Funds (No. 01030100004), and the Shenzhen Pengcheng Peacock Program (to EL). The establishment of the clinical cohort and genotyping was supported by the High Impact Research grant (HIR/MOHE; H-20001-E000001) to RR, SL, and AK.
Publisher Copyright:
Copyright © 2022 Han, Gulam, Zheng, Zulhaimi, Sia, He, Ho, Hadadi, Liu, Qin, Lobie, Kamarulzaman, Wang, Sandberg, Lewin, Rajasuriar and Leeansyah.
PY - 2022/10/20
Y1 - 2022/10/20
N2 - 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.
AB - 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.
KW - antiretroviral (ARV) therapy
KW - CD127 (IL7Ra) gene
KW - HIV-1
KW - IL-7
KW - MAIT cells
UR - http://www.scopus.com/inward/record.url?scp=85141221387&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2022.985385
DO - 10.3389/fimmu.2022.985385
M3 - Article
C2 - 36341446
AN - SCOPUS:85141221387
SN - 1664-3224
VL - 13
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 985385
ER -
