Research Progress of Natural Killer Cells in Hashimoto’s Thyroiditis

Yanchun Wang,1,* Zhangren Yan,2,* Jianhang Miao,3 Huafa Que,4 Wei Shan4 1College of Clinical Medicine, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China; 2Department of Traditional Chinese Medicine Surgery, The Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China; 3Department of General Surgery,Zhongshan City People’s Hospital, Zhongshan, Guangdong, People’s Republic of China; 4Traditional Chinese Medicine Surgery, Longhua Hospital Affiliated to Shanghai University of Chinese Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Shan, Traditional Chinese Medicine Surgery, Longhua Hospital Affiliated to Shanghai University of Chinese Medicine, No. 725 Wanping South Road, Shanghai, 200032, People’s Republic of China, Email [email protected]: Hashimoto’s thyroiditis is one of the most common autoimmune diseases, characterized by lymphocytic infiltration, thyroid autoantibody production, and progressive thyroid destruction. Natural killer cells, as innate immune effectors, play a dual role in HT pathogenesis through cytotoxicity, death receptor signaling, inflammasome activation, and secretion of proinflammatory cytokines. Recent studies using single-cell RNA sequencing have revealed functional heterogeneity of NK subsets, suggesting stage-specific roles in either amplifying or regulating inflammation. Moreover, peripheral blood from HT patients shows increased expression of activating receptors such as NKG2D and NKp30, positively correlated with thyroid autoantibody titers, while abnormal activation of the NLRP3 inflammasome drives NK cell–mediated IFN-γ release and thyroid follicular cell pyroptosis. These advances highlight NK cells as both contributors to immune imbalance and potential therapeutic targets. A better understanding of NK cell–related mechanisms will provide novel insights into disease monitoring and the development of targeted interventions for HT.Keywords: natural killer cells, hashimoto’s thyroiditis, receptor, cytotoxicity