biostudies-literatureUnknownAybar-Torres ANHLBI NIH HHSThe significance of STING (encoded by the <i>TMEM173</i> gene) in tissue inflammation and cancer immunotherapy has been increasingly recognized. Intriguingly, common human <i>TMEM173</i> alleles R71H-G230A-R293Q (<i>HAQ)</i> and G230A-R293Q (<i>AQ</i>) are carried by ~60% of East Asians and ~40% of Africans, respectively. Here, we examine the modulatory effects of <i>HAQ, AQ</i> alleles on STING-associated vasculopathy with onset in infancy (SAVI), an autosomal dominant, fatal inflammatory disease caused by gain-of-function human <i>STING</i> mutations. CD4 T cellpenia is evident in SAVI patients and mouse models. Using STING knock-in mice expressing common human <i>TMEM173</i> alleles <i>HAQ</i>, <i>AQ</i>, and <i>Q293</i>, we found that <i>HAQ, AQ</i>, and <i>Q293</i> splenocytes resist bioRxiv : the preprint server for biology2023.10.05.561109https://www.ebi.ac.uk/biostudies/studies/S-EPMC10602033biostudies-literatureThe common <i>TMEM173 HAQ, AQ</i> alleles rescue CD4 T cellpenia, restore T-regs, and prevent <i>SAVI (N153S)</i> inflammatory disease in mice.PMC10602033R01 HL152163Aybar-Torres ASharma AKPham ATSaldarriaga LAEmtiazjoo AMBryant AJJin LfalseThe common <i>TMEM173 HAQ, AQ</i> alleles rescue CD4 T cellpenia, restore T-regs, and prevent <i>SAVI (N153S)</i> inflammatory disease in mice.The significance of STING (encoded by the <i>TMEM173</i> gene) in tissue inflammation and cancer immunotherapy has been increasingly recognized. Intriguingly, common human <i>TMEM173</i> alleles R71H-G230A-R293Q (<i>HAQ)</i> and G230A-R293Q (<i>AQ</i>) are carried by ~60% of East Asians and ~40% of Africans, respectively. Here, we examine the modulatory effects of <i>HAQ, AQ</i> alleles on STING-associated vasculopathy with onset in infancy (SAVI), an autosomal dominant, fatal inflammatory disease caused by gain-of-function human <i>STING</i> mutations. CD4 T cellpenia is evident in SAVI patients and mouse models. Using STING knock-in mice expressing common human <i>TMEM173</i> alleles <i>HAQ</i>, <i>AQ</i>, and <i>Q293</i>, we found that <i>HAQ, AQ</i>, and <i>Q293</i> splenocytes resist 2024-01-01T00:00:00Z2024 Jun2026-04-08T13:29:06.833Z2025-08-24T03:08:41.247ZS-EPMC106020333788654710.1101/2023.10.05.561109