PMID- 22539788
OWN - NLM
STAT- MEDLINE
DCOM- 20120814
LR  - 20171116
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 188
IP  - 11
DP  - 2012 Jun 1
TI  - Dendritic cell-specific ablation of the protein tyrosine phosphatase Shp1 
      promotes Th1 cell differentiation and induces autoimmunity.
PG  - 5397-407
LID - 10.4049/jimmunol.1103210 [doi]
AB  - Dendritic cells (DCs) promote immune responses to foreign Ags and immune 
      tolerance to self-Ags. Deregulation of DCs is implicated in autoimmunity, but the 
      molecules that regulate DCs to protect against autoimmunity have remained 
      unknown. In this study, we show that mice lacking the protein tyrosine 
      phosphatase Shp1 specifically in DCs develop splenomegaly associated with more 
      CD11c(+) DCs. Splenic DCs from the mutant mice showed upregulation of CD86 and 
      CCR7 expression and of LPS-induced production of proinflammatory cytokines. The 
      mice manifested more splenic Th1 cells, consistent with the increased ability of 
      their DCs to induce production of IFN-gamma by Ag-specific T cells in vitro. The 
      number of splenic CD5(+)CD19(+) B-1a cells and the serum concentrations of Igs M 
      and G2a were also increased in the mutant mice. Moreover, aged mutant mice 
      developed glomerulonephritis and interstitial pneumonitis together with increased 
      serum concentrations of autoantibodies. Shp1 is thus a key regulator of DC 
      functions that protects against autoimmunity.
FAU - Kaneko, Tetsuya
AU  - Kaneko T
AD  - Laboratory of Biosignal Sciences, Institute for Molecular and Cellular 
      Regulation, Gunma University, Maebashi, Gunma 371-8512, Japan.
FAU - Saito, Yasuyuki
AU  - Saito Y
FAU - Kotani, Takenori
AU  - Kotani T
FAU - Okazawa, Hideki
AU  - Okazawa H
FAU - Iwamura, Hiroko
AU  - Iwamura H
FAU - Sato-Hashimoto, Miho
AU  - Sato-Hashimoto M
FAU - Kanazawa, Yoshitake
AU  - Kanazawa Y
FAU - Takahashi, Satoshi
AU  - Takahashi S
FAU - Hiromura, Keiju
AU  - Hiromura K
FAU - Kusakari, Shinya
AU  - Kusakari S
FAU - Kaneko, Yoriaki
AU  - Kaneko Y
FAU - Murata, Yoji
AU  - Murata Y
FAU - Ohnishi, Hiroshi
AU  - Ohnishi H
FAU - Nojima, Yoshihisa
AU  - Nojima Y
FAU - Takagishi, Kenji
AU  - Takagishi K
FAU - Matozaki, Takashi
AU  - Matozaki T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120425
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Autoantibodies)
RN  - 0 (CD11c Antigen)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 6)
RN  - EC 3.1.3.48 (Ptpn6 protein, mouse)
SB  - IM
MH  - Animals
MH  - Autoantibodies/biosynthesis
MH  - Autoimmune Diseases/*genetics/immunology/pathology
MH  - CD11c Antigen/biosynthesis
MH  - Cell Differentiation/genetics/*immunology
MH  - Dendritic Cells/*enzymology/*immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 
      6/*deficiency/*genetics/physiology
MH  - Splenomegaly/genetics/immunology/pathology
MH  - Th1 Cells/cytology/*immunology
MH  - Up-Regulation/genetics/immunology
EDAT- 2012/04/28 06:00
MHDA- 2012/08/15 06:00
CRDT- 2012/04/28 06:00
PHST- 2012/04/28 06:00 [entrez]
PHST- 2012/04/28 06:00 [pubmed]
PHST- 2012/08/15 06:00 [medline]
AID - jimmunol.1103210 [pii]
AID - 10.4049/jimmunol.1103210 [doi]
PST - ppublish
SO  - J Immunol. 2012 Jun 1;188(11):5397-407. doi: 10.4049/jimmunol.1103210. Epub 2012 
      Apr 25.