Abstract
Tissues accommodate defined numbers of dendritic cells (DCs) in highly specific niches where different intrinsic and environmental stimuli control DC life span and numbers. DC homeostasis in tissues is important, because experimental changes in DC numbers influence immunity and tolerance toward various immune catastrophes and inflammation. However, the precise molecular mechanisms regulating DC life span and homeostasis are unclear. We report that the GTPase RhoA controls homeostatic proliferation, cytokinesis, survival, and turnover of cDCs. Deletion of RhoA strongly decreased the numbers of CD11b(-)CD8(+) and CD11b(+)Esam(hi) DC subsets, whereas CD11b(+)Esam(lo) DCs were not affected in conditional RhoA-deficient mice. Proteome analyses revealed a defective prosurvival pathway via PI3K/protein kinase B (Akt1)/Bcl-2-associated death promoter in the absence of RhoA. Taken together, our findings identify RhoA as a central regulator of DC homeostasis, and its deletion decreases DC numbers below critical thresholds for immune protection and homeostasis, causing aberrant compensatory DC proliferation.
| Original language | English |
|---|---|
| Journal | Journal of immunology (Baltimore, Md. : 1950) |
| Volume | 195 |
| Issue number | 9 |
| Pages (from-to) | 4244-56 |
| Number of pages | 13 |
| ISSN | 0022-1767 |
| DOIs | |
| Publication status | Published - 1 Nov 2015 |
Keywords
- Animals
- Antigens, CD11c
- Apoptosis
- Blotting, Western
- Bone Marrow Cells
- Cell Proliferation
- Cell Survival
- Cells, Cultured
- Cytokinesis
- Dendritic Cells
- Flow Cytometry
- Homeostasis
- Membrane Proteins
- Mice, Knockout
- Mice, Transgenic
- Phosphatidylinositol 3-Kinases
- Proto-Oncogene Proteins c-akt
- Reverse Transcriptase Polymerase Chain Reaction
- Signal Transduction
- Spleen
- bcl-Associated Death Protein
- rhoA GTP-Binding Protein
- Journal Article
- Research Support, Non-U.S. Gov't