| First Author | Dong X | Year | 2019 |
| Journal | J Immunol | Volume | 202 |
| Issue | 11 | Pages | 3187-3197 |
| PubMed ID | 31028120 | Mgi Jnum | J:288641 |
| Mgi Id | MGI:6306235 | Doi | 10.4049/jimmunol.1900089 |
| Citation | Dong X, et al. (2019) Dlg1 Maintains Dendritic Cell Function by Securing Voltage-Gated K(+) Channel Integrity. J Immunol 202(11):3187-3197 |
| abstractText | 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 (Ca(2+)) influx events in DCs upon stimulation, both of which are known to be required for proper function of DCs. At a molecular level, Dlg1 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 Dlg1 and the voltage-gated K(+) channels axis in DC functions. |
