Blockade of Kv1.3 potassium channel inhibits CD8+ T cell‐mediated neuroinflammation via PD‐1/Blimp‐1 signaling. Issue 11 (27th September 2020)

• Record Type: Journal Article
• Authors: Zhao, Yipeng; Qiu, Wei; Liu, Junchen; Yuan, Xiaolu; Mao, Wenqian; Yin, Jun; Peng, BiWen; Liu, WanHong; Han, Song; He, XiaoHua
• Is Part Of: FASEB journal. Volume 34:Issue 11(2020)
• Page Start: 15492
• Page End: 15503
• Publication Date: 2020-09-27
• Subjects: Blimp‐1 -- CD8+ T cells -- EAE -- Kv1.3 channel -- PD‐1; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202000861RR
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: Kv1.3 potassium channel is considered as a target for the treatment of autoimmune diseases such as multiple sclerosis (MS), since Kv1.3 blockade suppresses memory T cell activation including cytotoxic CD8 + T cells. However, the underlying signaling pathway related to autoimmune CD8 + T cell inhibition by Kv1.3 channel in neuroinflammatory diseases remains unclear. We found that ImK, a selective Kv1.3 blocker, reduced auto‐reactive CD8 + T cell infiltration in the spinal cords of experimental autoimmune encephalomyelitis (EAE) rats, an animal model of MS. ImK suppressed transcriptional factor Blimp‐1 expression and reduced the cytotoxicity of CD8 + T cells on neuronal cells. Furthermore, ImK upregulated co‐inhibitory molecule PD‐1 to inhibit B lymphocyte‐induced maturation protein (Blimp‐1) in an IL‐2 independent way. In addition, PD‐1 inhibitor impaired the suppression of ImK on CD8 + T cells and accelerated EAE progression. Our study demonstrated a novel regulatory mechanism of Kv1.3 blockade on modulating CD8 + T cell differentiation through PD‐1/Blimp‐1 signaling. This work expands the understanding of Kv1.3 channel for modulating neuroinflammation.