Allograft Inflammatory Factor-1 Governs Hematopoietic Stem Cell Differentiation Into cDC1 and Monocyte-Derived Dendritic Cells Through IRF8 and RelB in vitro
| Autor: | Apollo D. Kacsinta, Tatiana Rodrigues de Moura, Diana M. Elizondo, Nailah Z. D. Brandy, Michael W. Lipscomb, Naomi L. Haddock, Ricardo L. Louzada da Silva L. Louzada da Silva |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine RelB/NFκB p38 Mitogen-Activated Protein Kinases Monocytes Mice 0302 clinical medicine Immunology and Allergy RNA Small Interfering Cells Cultured Protein Kinase C Original Research education.field_of_study Hematopoietic stem cell differentiation protein kinase C (PKC) RELB Microfilament Proteins IRF8 transcriptional coactivator Cell Differentiation Cell biology Haematopoiesis Gene Knockdown Techniques Interferon Regulatory Factors Allograft inflammatory factor 1 Female Stem cell lcsh:Immunologic diseases. Allergy Immunology Bone Marrow Cells Biology Transfection 03 medical and health sciences allograft inflammatory factor 1 Animals dendritic cells Progenitor cell education monocyte-derived DC Calcium-Binding Proteins Transcription Factor RelB Granulocyte-Macrophage Colony-Stimulating Factor Membrane Proteins NF-kappa B p50 Subunit Dendritic cell cDC1 dendritic cells Hematopoiesis hematopoietic stem cells Mice Inbred C57BL 030104 developmental biology IRF8 lcsh:RC581-607 030215 immunology |
| Zdroj: | Frontiers in Immunology, Vol 10 (2019) Frontiers in Immunology |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2019.00173/full |
| Popis: | The multistep differentiation process from hematopoietic stem cells through common myeloid progenitors into committed dendritic cell (DC) subsets remains to be fully addressed. These studies now show that Allograft Inflammatory Factor-1 (AIF1) is required for differentiation of classical DC type 1 (cDC1) subsets and monocyte-derived DC (Mo-DC). Phenotypic studies found that AIF1 expression increased in committed subsets differentiating from common myeloid progenitors (CMP). However, silencing AIF1 expression in hematopoietic stem progenitors restrained the capacity to differentiate into Mo-DC and cDC1 cell subsets under GM-CSF or Flt3-L stimuli conditions, respectively. This was further marked by restrained expression of IRF8, which is critical for development of Mo-DC and cDC1 subsets. As a result, absence of AIF1 restrained the cells at the Lin−CD117+FcγR−CD34+ CMP stage. Further biochemical studies revealed that abrogating AIF1 resulted in inhibition of the NFκB family member RelB expression and p38 MAPK phosphorylation during differentiation of Mo-DC. Lastly, protein binding studies identified that AIF1 interacts with protein kinase C (PKC) to influence downstream signaling pathways. Taken together, this is the first report showing a novel role of AIF1 as a calcium-responsive scaffold protein that supports IRF8 expression and interacts with PKC to drive NFκB-related RelB for successfully differentiating hematopoietic progenitor cells into cDC and Mo-DC subsets under Flt3-L and GM-CSF stimuli, respectively. |
| Databáze: | OpenAIRE |
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