| Title | Dlg1 Maintains Dendritic Cell Function by Securing Voltage-Gated K+ Channel Integrity |
| Authors | Dong, Xuejiao Wei, Lisi Guo, Xueheng Yang, Zhiyong Wu, Chuan Li, Peiyu Lu, Lu Qi, Hai Shi, Yan Hu, Xiaoyu Wu, Li Chen, Liangyi Liu, Wanli |
| Affiliation | Tsinghua Univ, Minist Educ,Inst Immunol, Key Lab Prot Sci,Sch Life Sci,Beijing Key Lab Imm, Ctr Life Sci,Collaborat Innovat Ctr Diag & Treatm, Beijing 100084, Peoples R China Peking Univ, State Key Lab Membrane Biol, Beijing Key Lab Cardiometab Mol Med, Inst Mol Med, Beijing 100871, Peoples R China Tsinghua Univ, Inst Immunol, Sch Med, Beijing 100084, Peoples R China Natl Educ Examinat Author, Beijing 100084, Peoples R China Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA NCI, Expt Immunol Branch, NIH, Bethesda, MD 20851 USA Fudan Univ, Key Lab Med Mol Virol, Minist Educ, Minist Hlth,Sch Basic Med Sci, Shanghai 200032, Peoples R China Fudan Univ, Shanghai Publ Hlth Clin Ctr, Shanghai 200032, Peoples R China Guangdong Med Univ, Dept Infect Dis, Shenzhen Nanshan Peoples Hosp, Shenzhen 518052, Peoples R China Guangdong Med Univ, Shenzhen Key Lab Endogenous Infect, Shenzhen Nanshan Peoples Hosp, Shenzhen 518052, Peoples R China |
| Issue Date | 2019 |
| Publisher | JOURNAL OF IMMUNOLOGY |
| Abstract | Dendritic cells (DCs) play key roles in Ab responses by presenting Ags to lymphocytes and by producing proinflammatory cytokines. In this study, we reported that DC-specific knockout of discs large homologue 1 (Dlg1) resulted in a significantly reduced capacity to mediate Ab responses to both thymus-independent and thymus-dependent Ags in Dlg1(fl/fl)Cd11c-Cre-GFP mice. Mechanistically, Dlg1-deficient DCs showed severely impaired endocytosis and phagocytosis capacities upon Ag exposure. In parallel, loss of Dlg1 significantly jeopardized the proinflammatory cytokine production by DCs upon TLR stimulation. Thus, Dlg1-deficient DCs lost their functions to support innate and adaptive immunities. At a cellular level, Dlg1 exhibited an indispensable function to maintain membrane potential changes by securing potassium ion (K+) efflux and subsequent calcium ion (Ca2+) influx events in DCs upon stimulation, both of which are known to be required for proper function of DCs. At a molecular level, Dlgl did so by retaining the integrity of voltage-gated K+ channels (including Kv1.3) in DCs. The loss of Dlg1 led to a decreased expression of K+ channels, resulting in impaired membrane potential changes and, as a consequence, reduced proinflammatory cytokine production, compromised Ag endocytosis, and phagocytosis. In conclusion, this study provided, to our knowledge, a novel insight into Dlgl and the voltage-gated K+ channels axis in DC functions. |
| URI | http://hdl.handle.net/20.500.11897/547991 |
| ISSN | 0022-1767 |
| DOI | 10.4049/jimmunol.1900089 |
| Indexed | SCI(E) EI |
| Appears in Collections: | 分子医学研究所 膜生物学国家重点实验室 |
