| First Author | Calmette J | Year | 2016 |
| Journal | J Immunol | Volume | 197 |
| Issue | 11 | Pages | 4247-4256 |
| PubMed ID | 27793999 | Mgi Jnum | J:290514 |
| Mgi Id | MGI:6443849 | Doi | 10.4049/jimmunol.1600561 |
| Citation | Calmette J, et al. (2016) Glucocorticoid-Induced Leucine Zipper Protein Controls Macropinocytosis in Dendritic Cells. J Immunol 197(11):4247-4256 |
| abstractText | Ag sampling is a key process in dendritic cell (DC) biology. DCs use constitutive macropinocytosis, receptor-mediated endocytosis, and phagocytosis to capture exogenous Ags for presentation to T cells. We investigated the mechanisms that regulate Ag uptake by DCs in the steady-state and after a short-term LPS exposure in vitro and in vivo. We show that the glucocorticoid-induced leucine zipper protein (GILZ), already known to regulate effector versus regulatory T cell activation by DCs, selectively limits macropinocytosis, but not receptor-mediated phagocytosis, in immature and recently activated DCs. In vivo, the GILZ-mediated inhibition of Ag uptake is restricted to the CD8alpha(+) DC subset, which expresses the highest GILZ level among splenic DC subsets. In recently activated DCs, we further establish that GILZ limits p38 MAPK phosphorylation, providing a possible mechanism for GILZ-mediated macropinocytosis control. Finally, our results demonstrate that the modulation of Ag uptake by GILZ does not result in altered Ag presentation to CD4 T cells but impacts the efficiency of cross-presentation to CD8 T cells. Altogether, our results identify GILZ as an endogenous inhibitor of macropinocytosis in DCs, the action of which contributes to the fine-tuning of Ag cross-presentation. |
