Cargando…

Allograft Inflammatory Factor-1 Governs Hematopoietic Stem Cell Differentiation Into cDC1 and Monocyte-Derived Dendritic Cells Through IRF8 and RelB in vitro

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 (...

Descripción completa

Detalles Bibliográficos
Autores principales: Elizondo, Diana M., Brandy, Nailah Z. D., da Silva, Ricardo L. L., Haddock, Naomi L., Kacsinta, Apollo D., de Moura, Tatiana R., Lipscomb, Michael W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375893/
https://www.ncbi.nlm.nih.gov/pubmed/30800127
http://dx.doi.org/10.3389/fimmu.2019.00173
_version_ 1783395439515533312
author Elizondo, Diana M.
Brandy, Nailah Z. D.
da Silva, Ricardo L. L.
Haddock, Naomi L.
Kacsinta, Apollo D.
de Moura, Tatiana R.
Lipscomb, Michael W.
author_facet Elizondo, Diana M.
Brandy, Nailah Z. D.
da Silva, Ricardo L. L.
Haddock, Naomi L.
Kacsinta, Apollo D.
de Moura, Tatiana R.
Lipscomb, Michael W.
author_sort Elizondo, Diana M.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6375893
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-63758932019-02-22 Allograft Inflammatory Factor-1 Governs Hematopoietic Stem Cell Differentiation Into cDC1 and Monocyte-Derived Dendritic Cells Through IRF8 and RelB in vitro Elizondo, Diana M. Brandy, Nailah Z. D. da Silva, Ricardo L. L. Haddock, Naomi L. Kacsinta, Apollo D. de Moura, Tatiana R. Lipscomb, Michael W. Front Immunol Immunology 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. Frontiers Media S.A. 2019-02-08 /pmc/articles/PMC6375893/ /pubmed/30800127 http://dx.doi.org/10.3389/fimmu.2019.00173 Text en Copyright © 2019 Elizondo, Brandy, da Silva, Haddock, Kacsinta, de Moura and Lipscomb. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Elizondo, Diana M.
Brandy, Nailah Z. D.
da Silva, Ricardo L. L.
Haddock, Naomi L.
Kacsinta, Apollo D.
de Moura, Tatiana R.
Lipscomb, Michael W.
Allograft Inflammatory Factor-1 Governs Hematopoietic Stem Cell Differentiation Into cDC1 and Monocyte-Derived Dendritic Cells Through IRF8 and RelB in vitro
title Allograft Inflammatory Factor-1 Governs Hematopoietic Stem Cell Differentiation Into cDC1 and Monocyte-Derived Dendritic Cells Through IRF8 and RelB in vitro
title_full Allograft Inflammatory Factor-1 Governs Hematopoietic Stem Cell Differentiation Into cDC1 and Monocyte-Derived Dendritic Cells Through IRF8 and RelB in vitro
title_fullStr Allograft Inflammatory Factor-1 Governs Hematopoietic Stem Cell Differentiation Into cDC1 and Monocyte-Derived Dendritic Cells Through IRF8 and RelB in vitro
title_full_unstemmed Allograft Inflammatory Factor-1 Governs Hematopoietic Stem Cell Differentiation Into cDC1 and Monocyte-Derived Dendritic Cells Through IRF8 and RelB in vitro
title_short Allograft Inflammatory Factor-1 Governs Hematopoietic Stem Cell Differentiation Into cDC1 and Monocyte-Derived Dendritic Cells Through IRF8 and RelB in vitro
title_sort allograft inflammatory factor-1 governs hematopoietic stem cell differentiation into cdc1 and monocyte-derived dendritic cells through irf8 and relb in vitro
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375893/
https://www.ncbi.nlm.nih.gov/pubmed/30800127
http://dx.doi.org/10.3389/fimmu.2019.00173
work_keys_str_mv AT elizondodianam allograftinflammatoryfactor1governshematopoieticstemcelldifferentiationintocdc1andmonocytederiveddendriticcellsthroughirf8andrelbinvitro
AT brandynailahzd allograftinflammatoryfactor1governshematopoieticstemcelldifferentiationintocdc1andmonocytederiveddendriticcellsthroughirf8andrelbinvitro
AT dasilvaricardoll allograftinflammatoryfactor1governshematopoieticstemcelldifferentiationintocdc1andmonocytederiveddendriticcellsthroughirf8andrelbinvitro
AT haddocknaomil allograftinflammatoryfactor1governshematopoieticstemcelldifferentiationintocdc1andmonocytederiveddendriticcellsthroughirf8andrelbinvitro
AT kacsintaapollod allograftinflammatoryfactor1governshematopoieticstemcelldifferentiationintocdc1andmonocytederiveddendriticcellsthroughirf8andrelbinvitro
AT demouratatianar allograftinflammatoryfactor1governshematopoieticstemcelldifferentiationintocdc1andmonocytederiveddendriticcellsthroughirf8andrelbinvitro
AT lipscombmichaelw allograftinflammatoryfactor1governshematopoieticstemcelldifferentiationintocdc1andmonocytederiveddendriticcellsthroughirf8andrelbinvitro