Soluble galectin 9 potently enhanced regulatory T‐cell formation, a pathway impaired in patients with intracranial aneurysm

摘要

Summary Patients with intracranial aneurysm (IA) present a dysregulated immune system with lower frequency of regulatory T (Treg) cells. Here, we examined whether galectin 9 (Gal‐9), the natural ligand of Tim‐3, could promote Treg cells in IA patients. We first discovered that the intracellular and extracellular Gal‐9 was primarily expressed by CD4 + CD25 ? T conventional (Tconv) cells, and also by monocytes at lower levels, but rarely by CD4 + CD25 + Treg cells. In IA patients, the Gal‐9 expression was significantly lower than in healthy controls. CD4 + CD25 ? Tconv cells could be induced into Foxp3‐expressing induced Treg (iTreg) cells using a TGF‐β‐containing milieu. We found that soluble Gal‐9 significantly enhanced this process by potently upregulating the expression of Foxp3, IL‐10 and TGF‐β in a concentration‐dependent manner. In addition, in the absence of additional Gal‐9, the level of Foxp3 upregulation was directly correlated with the level of intrinsic Gal‐9 expression. Notably, the strength of external Gal‐9‐mediated effects was significantly lower in IA patients than in healthy controls. Using a Tim‐3 blocking antibody, we found that the promotion of iTreg development by soluble Gal‐9 was dependent on the Tim‐3 signalling pathway. Overall, our investigations demonstrated that Gal‐9 presented a critical role in the development of iTreg cells. However, this mechanism was impaired in IA patients due to lower expression of both Gal‐9 and Tim‐3.