The common TMEM173 HAQ, AQ alleles rescue CD4 T cellpenia, restore T-regs, and prevent SAVI (N153S) inflammatory disease in mice.

ABSTRACT: The significance of STING (encoded by the TMEM173 gene) in tissue inflammation and cancer immunotherapy has been increasingly recognized. Intriguingly, common human TMEM173 alleles R71H-G230A-R293Q (HAQ) and G230A-R293Q (AQ) are carried by ~60% of East Asians and ~40% of Africans, respectively. Here, we examine the modulatory effects of HAQ, AQ alleles on STING-associated vasculopathy with onset in infancy (SAVI), an autosomal dominant, fatal inflammatory disease caused by gain-of-function human STING mutations. CD4 T cellpenia is evident in SAVI patients and mouse models. Using STING knock-in mice expressing common human TMEM173 alleles HAQ, AQ, and Q293, we found that HAQ, AQ, and Q293 splenocytes resist

SUBMITTER: Aybar-Torres A 

PROVIDER: S-EPMC10602033 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature