Stat6, Signal Transducer and Activator of Transcription 6, is a transcription factor. Primarily stimulated by interleukin(IL)-4 and IL-13, it acts as a T helper type 2 (Th2)-inducing factor. The STAT6 signaling pathway is implicated in the pathophysiology of various allergic conditions, tumor microenvironment regulation, and some forms of lymphomas [2].

In stroke mouse models, STAT6 deficiency led to reduced clearance of dead/dying neurons, increased inflammatory gene signature in microglia/macrophages, enlarged infarct volume, increased brain tissue loss, and exacerbated long-term functional deficits. This indicates that STAT6 activation in microglia and macrophages is essential for neuroprotection, and STAT6/Arg1 signaling axis modulates microglia/macrophage phenotype, accelerates inflammation resolution, and improves stroke outcomes [1].

In keloid fibroblasts, downregulation of IL-13RA2 led to activation of JAK/STAT6, promoting cell proliferation, migration, etc., while inhibition of p-STAT6 could alleviate keloid-like phenotypes [3].

In glyoxylate-induced kidney stone mice, STAT6 promoted renal fibrosis by mediating macrophage-to-myofibroblast transition via inhibiting fatty acid oxidation, and pharmacological inhibition of STAT6 prevented the development of renal injury and fibrosis [4].

In conclusion, Stat6 is crucial in regulating immune-related responses and inflammation. Through gene knockout (KO) or conditional knockout (CKO) mouse models, its role in diseases such as stroke, keloid fibrosis, and renal fibrosis has been revealed. Understanding Stat6's function provides potential therapeutic targets for these diseases.