Dendritic Cell Reprogramming by Endogenously Produced Lactic Acid
| Autor: | Bence Rethi, Craig E. Wheelock, Éva Rajnavölgyi, Nancy Vivar, Tünde Fekete, Anca I. Catrina, Stuart G. Snowden, Aikaterini Nasi, Akilan Krishnamurthy |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Chemokine
biology T cell Immunology Cell CCL19 Cell Culture Techniques Cell Differentiation Enzyme-Linked Immunosorbent Assay Dendritic Cells Dendritic cell Flow Cytometry Polymerase Chain Reaction Cell biology Proinflammatory cytokine Autocrine Communication medicine.anatomical_structure Cell culture biology.protein medicine Humans Immunology and Allergy Lactic Acid Transcriptome Autocrine signalling |
| Zdroj: | The Journal of Immunology. 191:3090-3099 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1300772 |
| Popis: | The demand for controlling T cell responses via dendritic cell (DC) vaccines initiated a quest for reliable and feasible DC modulatory strategies that would facilitate cytotoxicity against tumors or tolerance in autoimmunity. We studied endogenous mechanisms in developing monocyte-derived DCs (MoDCs) that can induce inflammatory or suppressor programs during differentiation, and we identified a powerful autocrine pathway that, in a cell concentration–dependent manner, strongly interferes with inflammatory DC differentiation. MoDCs developing at low cell culture density have superior ability to produce inflammatory cytokines, to induce Th1 polarization, and to migrate toward the lymphoid tissue chemokine CCL19. On the contrary, MoDCs originated from dense cultures produce IL-10 but no inflammatory cytokines upon activation. DCs from high-density cultures maintained more differentiation plasticity and can develop to osteoclasts. The cell concentration–dependent pathway was independent of peroxisome proliferator–activated receptor γ (PPARγ), a known endogenous regulator of MoDC differentiation. Instead, it acted through lactic acid, which accumulated in dense cultures and induced an early and long-lasting reprogramming of MoDC differentiation. Our results suggest that the lactic acid–mediated inhibitory pathway could be efficiently manipulated in developing MoDCs to influence the immunogenicity of DC vaccines. |
| Databáze: | OpenAIRE |
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