PMID- 28890536
OWN - NLM
STAT- MEDLINE
DCOM- 20180702
LR  - 20181113
IS  - 1440-1711 (Electronic)
IS  - 0818-9641 (Print)
IS  - 0818-9641 (Linking)
VI  - 95
IP  - 10
DP  - 2017 Nov
TI  - A key role for IL-7R in the generation of microenvironments required for thymic 
      dendritic cells.
PG  - 933-942
LID - 10.1038/icb.2017.74 [doi]
AB  - Interleukin-7 receptor (IL-7R) signaling is critical for multiple stages of 
      T-cell development, but a role in the establishment of the mature thymic 
      architecture needed for T-cell development and thymocyte selection has not been 
      established. Crosstalk signals between developing thymocytes and thymic 
      epithelial cell (TEC) precursors are critical for their differentiation into 
      cortical TECs (cTECs) and medullary TECs (mTECs). In addition, mTEC-derived 
      factors have been implicated in the recruitment of thymic dendritic cells (DCs) 
      and intrathymic DC development. We therefore examined corticomedullary structure 
      and DC populations in the thymus of Il7r(-/-) mice. Analysis of TEC phenotype and 
      spatial organization revealed a striking shift in the mTEC to cTEC ratio, 
      accompanied by disorganized corticomedullary structure. Several of the thymic 
      subsets known to have DC potential were nearly absent, accompanied by reductions 
      in DC cell numbers. We also examined chemokine expression in the Il7r(-/-) 
      thymus, and found a significant decrease in mTEC-derived CCR7 ligand expression, 
      and high levels of cTEC-derived chemokines, including CCL25 and CXCL12. Although 
      splenic DCs were similarly affected, bone marrow (BM) precursors capable of 
      giving rise to DCs were unperturbed. Finally, BM chimeras showed that there was 
      no intrinsic need for IL-7R signaling in the development or recruitment of thymic 
      DCs, but that the provision of wild-type progenitors enhanced reconstitution of 
      thymic DCs from Il7r(-/-) progenitors. Our results are therefore supportive of a 
      model in which Il7r-dependent cells are required to set up the microenvironments 
      that allow accumulation of thymic DCs.
FAU - Moore, Amanda J
AU  - Moore AJ
AD  - Biological Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
AD  - Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
FAU - In, Tracy Sh
AU  - In TS
AD  - Biological Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
AD  - Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
FAU - Trotman-Grant, Ashton
AU  - Trotman-Grant A
AD  - Biological Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
AD  - Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
FAU - Yoganathan, Kogulan
AU  - Yoganathan K
AD  - Biological Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
AD  - Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
FAU - Montpellier, Bertrand
AU  - Montpellier B
AD  - Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
AD  - Program in Developmental and Stem Cell Biology, Hospital for Sick Children 
      Research Institute, Toronto, Ontario, Canada.
FAU - Guidos, Cynthia J
AU  - Guidos CJ
AUID- ORCID: 0000-0002-7674-2612
AD  - Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
AD  - Program in Developmental and Stem Cell Biology, Hospital for Sick Children 
      Research Institute, Toronto, Ontario, Canada.
FAU - Zuniga-Pflucker, Juan Carlos
AU  - Zuniga-Pflucker JC
AUID- ORCID: 0000-0003-2538-3178
AD  - Biological Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
AD  - Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
FAU - Anderson, Michele K
AU  - Anderson MK
AUID- ORCID: 0000-0002-8820-5910
AD  - Biological Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
AD  - Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
LA  - eng
GR  - P01 AI102853/AI/NIAID NIH HHS/United States
GR  - MOP 82861/CIHR/Canada
GR  - MOP 119538/CIHR/Canada
GR  - MOP11530/CIHR/Canada
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20170911
PL  - United States
TA  - Immunol Cell Biol
JT  - Immunology and cell biology
JID - 8706300
RN  - 0 (Ccl25 protein, mouse)
RN  - 0 (Ccr7 protein, mouse)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Chemokines, CC)
RN  - 0 (Receptors, CCR7)
RN  - 0 (Receptors, Interleukin-7)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Cellular Microenvironment
MH  - Chemokine CXCL12/metabolism
MH  - Chemokines, CC/metabolism
MH  - Dendritic Cells/*physiology
MH  - Epithelial Cells/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Receptors, CCR7/metabolism
MH  - Receptors, Interleukin-7/genetics/*metabolism
MH  - T-Lymphocytes/*physiology
MH  - Thymus Gland/*immunology
PMC - PMC5698111
MID - NIHMS901805
COIS- The authors declare no conflict of interest.
EDAT- 2017/09/12 06:00
MHDA- 2018/07/03 06:00
PMCR- 2017/11/27
CRDT- 2017/09/12 06:00
PHST- 2016/11/19 00:00 [received]
PHST- 2017/08/10 00:00 [revised]
PHST- 2017/08/24 00:00 [accepted]
PHST- 2017/09/12 06:00 [pubmed]
PHST- 2018/07/03 06:00 [medline]
PHST- 2017/09/12 06:00 [entrez]
PHST- 2017/11/27 00:00 [pmc-release]
AID - icb201774 [pii]
AID - 10.1038/icb.2017.74 [doi]
PST - ppublish
SO  - Immunol Cell Biol. 2017 Nov;95(10):933-942. doi: 10.1038/icb.2017.74. Epub 2017 
      Sep 11.