PMID- 25024389
OWN - NLM
STAT- MEDLINE
DCOM- 20141021
LR  - 20201209
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 193
IP  - 4
DP  - 2014 Aug 15
TI  - Lnk/Sh2b3 controls the production and function of dendritic cells and regulates 
      the induction of IFN-gamma-producing T cells.
PG  - 1728-36
LID - 10.4049/jimmunol.1303243 [doi]
AB  - Dendritic cells (DCs) are proficient APCs that play crucial roles in the immune 
      responses to various Ags and pathogens and polarize Th cell immune responses. 
      Lnk/SH2B adaptor protein 3 (Sh2b3) is an intracellular adaptor protein that 
      regulates B lymphopoiesis, megakaryopoiesis, and expansion of hematopoietic stem 
      cells by constraining cytokine signals. Recent genome-wide association studies 
      have revealed a link between polymorphism in this adaptor protein and autoimmune 
      diseases, including type 1 diabetes and celiac disease. We found that Lnk/Sh2b3 
      was also expressed in DCs and investigated its role in the production and 
      function of DC lineage cells. In Lnk(-/-) mice, DC numbers were increased in the 
      spleen and lymph nodes, and growth responses of bone marrow-derived DCs to GM-CSF 
      were augmented. Mature DCs from Lnk(-/-) mice were hypersensitive and showed 
      enhanced responses to IL-15 and GM-CSF. Compared to normal DCs, Lnk(-/-) DCs had 
      enhanced abilities to support the differentiation of IFN-gamma-producing Th1 cells 
      from naive CD4(+) T cells. This was due to their elevated expression of IL-12Rbeta1 
      and increased production of IFN-gamma. Lnk(-/-) DCs supported the appearance of 
      IFN-gamma-producing T cells even under conditions in which normal DCs supported 
      induction of regulatory T cells. These results indicated that Lnk/Sh2b3 plays a 
      regulatory role in the expansion of DCs and might influence inflammatory immune 
      responses in peripheral lymphoid tissues.
CI  - Copyright (c) 2014 by The American Association of Immunologists, Inc.
FAU - Mori, Taizo
AU  - Mori T
AD  - Department of Immune Regulation, Research Institute, National Center for Global 
      Health and Medicine, Chiba 272-8516, Japan;
FAU - Iwasaki, Yukiko
AU  - Iwasaki Y
AD  - Department of Immune Regulation, Research Institute, National Center for Global 
      Health and Medicine, Chiba 272-8516, Japan; Department of Allergy and 
      Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, 
      Japan;
FAU - Seki, Yoichi
AU  - Seki Y
AD  - Department of Immune Regulation, Research Institute, National Center for Global 
      Health and Medicine, Chiba 272-8516, Japan;
FAU - Iseki, Masanori
AU  - Iseki M
AD  - Department of Immune Regulation, Research Institute, National Center for Global 
      Health and Medicine, Chiba 272-8516, Japan;
FAU - Katayama, Hiroko
AU  - Katayama H
AD  - Department of Immune Regulation, Research Institute, National Center for Global 
      Health and Medicine, Chiba 272-8516, Japan;
FAU - Yamamoto, Kazuhiko
AU  - Yamamoto K
AD  - Department of Allergy and Rheumatology, Graduate School of Medicine, University 
      of Tokyo, Tokyo 113-8655, Japan;
FAU - Takatsu, Kiyoshi
AU  - Takatsu K
AD  - Department of Immunobiology and Pharmacological Genetics, Graduate School of 
      Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama 
      930-0194, Japan; and Prefectural Institute for Pharmaceutical Research, Toyama 
      939-0363, Japan.
FAU - Takaki, Satoshi
AU  - Takaki S
AD  - Department of Immune Regulation, Research Institute, National Center for Global 
      Health and Medicine, Chiba 272-8516, Japan; lbstakaki@hospk.ncgm.go.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140714
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Il12rb1 protein, mouse)
RN  - 0 (Interleukin-15)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Lnk protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, Interleukin-12)
RN  - 0 (flt3 ligand protein)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Adjuvants, Immunologic/pharmacology
MH  - Animals
MH  - Bone Marrow Cells/cytology
MH  - Celiac Disease/immunology
MH  - Cell Differentiation/immunology
MH  - Cells, Cultured
MH  - Dendritic Cells/*immunology
MH  - Diabetes Mellitus, Type 1/immunology
MH  - Genome-Wide Association Study
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology
MH  - Hematopoietic Stem Cells/immunology
MH  - Inflammation/immunology
MH  - Interferon-gamma/*biosynthesis
MH  - Interleukin-12/pharmacology
MH  - Interleukin-15/pharmacology
MH  - Intracellular Signaling Peptides and Proteins/biosynthesis/*genetics
MH  - Lymph Nodes/cytology
MH  - Lymphocyte Activation/immunology
MH  - Lymphopoiesis/*immunology
MH  - Membrane Proteins/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Polymorphism, Single Nucleotide
MH  - Receptors, Interleukin-12/biosynthesis
MH  - Spleen/cytology
MH  - T-Lymphocytes, Regulatory/immunology
MH  - Th1 Cells/*immunology
MH  - Thrombopoiesis/immunology
EDAT- 2014/07/16 06:00
MHDA- 2014/10/22 06:00
CRDT- 2014/07/16 06:00
PHST- 2014/07/16 06:00 [entrez]
PHST- 2014/07/16 06:00 [pubmed]
PHST- 2014/10/22 06:00 [medline]
AID - jimmunol.1303243 [pii]
AID - 10.4049/jimmunol.1303243 [doi]
PST - ppublish
SO  - J Immunol. 2014 Aug 15;193(4):1728-36. doi: 10.4049/jimmunol.1303243. Epub 2014 
      Jul 14.