PMID- 30333120
OWN - NLM
STAT- MEDLINE
DCOM- 20190910
LR  - 20210202
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 133
IP  - 4
DP  - 2019 Jan 24
TI  - Murine myeloproliferative disorder as a consequence of impaired collaboration 
      between dendritic cells and CD4 T cells.
PG  - 319-330
LID - 10.1182/blood-2018-05-850321 [doi]
AB  - Dendritic cells (DCs) are a key cell type in the initiation of the adaptive 
      immune response. Recently, an additional role for DCs in suppressing 
      myeloproliferation was discovered. Myeloproliferative disorder (MPD) was observed 
      in murine studies with constitutive depletion of DCs, as well as in patients with 
      congenital deficiency in DCs caused by mutations in GATA2 or IRF8 The mechanistic 
      link between DC deficiency and MPD was not predicted through the known biology 
      and has remained an enigma. Prevailing models suggest numerical DC deficiency 
      leads to MPD through compensatory myeloid differentiation. Here, we formally 
      tested whether MPD can also arise through a loss of DC function without numerical 
      deficiency. Using mice whose DCs are deficient in antigen presentation, we find 
      spontaneous MPD that is characterized by splenomegaly, neutrophilia, and 
      extramedullary hematopoiesis, despite normal numbers of DCs. Disease development 
      was dependent on loss of the MHC class II (MHCII) antigen-presenting complex on 
      DCs and was eliminated in mice deficient in total lymphocytes. Mice lacking MHCII 
      and CD4 T cells did not develop disease. Thus, MPD was paradoxically contingent 
      on the presence of CD4 T cells and on a failure of DCs to activate CD4 T cells, 
      trapping the cells in a naive Flt3 ligand-expressing state. These results 
      identify a novel requirement for intercellular collaboration between DCs and CD4 
      T cells to regulate myeloid differentiation. Our findings support a new 
      conceptual framework of DC biology in preventing MPD in mice and humans.
CI  - (c) 2019 by The American Society of Hematology.
FAU - Humblet-Baron, Stephanie
AU  - Humblet-Baron S
AUID- ORCID: 0000-0003-4684-069X
AD  - Vlaams Instituut voor Biotechnologie Center for Brain and Disease Research, 
      Leuven, Belgium.
AD  - Department of Microbiology and Immunology, KU Leuven-University of Leuven, 
      Leuven, Belgium; and.
FAU - Barber, John S
AU  - Barber JS
AD  - Vlaams Instituut voor Biotechnologie Center for Brain and Disease Research, 
      Leuven, Belgium.
AD  - Department of Microbiology and Immunology, KU Leuven-University of Leuven, 
      Leuven, Belgium; and.
FAU - Roca, Carlos P
AU  - Roca CP
AUID- ORCID: 0000-0003-0230-1926
AD  - Vlaams Instituut voor Biotechnologie Center for Brain and Disease Research, 
      Leuven, Belgium.
AD  - Department of Microbiology and Immunology, KU Leuven-University of Leuven, 
      Leuven, Belgium; and.
FAU - Lenaerts, Aurelie
AU  - Lenaerts A
AD  - Vlaams Instituut voor Biotechnologie Center for Brain and Disease Research, 
      Leuven, Belgium.
AD  - Department of Microbiology and Immunology, KU Leuven-University of Leuven, 
      Leuven, Belgium; and.
FAU - Koni, Pandelakis A
AU  - Koni PA
AD  - Georgia Cancer Center, Augusta University, Augusta, GA.
FAU - Liston, Adrian
AU  - Liston A
AUID- ORCID: 0000-0002-6272-4085
AD  - Vlaams Instituut voor Biotechnologie Center for Brain and Disease Research, 
      Leuven, Belgium.
AD  - Department of Microbiology and Immunology, KU Leuven-University of Leuven, 
      Leuven, Belgium; and.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181017
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (CD11c Antigen)
SB  - IM
MH  - Animals
MH  - CD11c Antigen/metabolism
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - *Cell Communication
MH  - Dendritic Cells/*immunology
MH  - Lymphocyte Activation/immunology
MH  - Mice, Inbred C57BL
MH  - Myeloid Cells/pathology
MH  - Myeloproliferative Disorders/*immunology/pathology
PMC - PMC6356150
COIS- Conflict-of-interest disclosure: The authors declare no competing financial 
      interests.
EDAT- 2018/10/20 06:00
MHDA- 2019/09/11 06:00
PMCR- 2019/01/24
CRDT- 2018/10/19 06:00
PHST- 2018/05/09 00:00 [received]
PHST- 2018/10/14 00:00 [accepted]
PHST- 2018/10/20 06:00 [pubmed]
PHST- 2019/09/11 06:00 [medline]
PHST- 2018/10/19 06:00 [entrez]
PHST- 2019/01/24 00:00 [pmc-release]
AID - S0006-4971(20)42845-9 [pii]
AID - 2018/850321 [pii]
AID - 10.1182/blood-2018-05-850321 [doi]
PST - ppublish
SO  - Blood. 2019 Jan 24;133(4):319-330. doi: 10.1182/blood-2018-05-850321. Epub 2018 
      Oct 17.