PMID- 31000202
OWN - NLM
STAT- MEDLINE
DCOM- 20200623
LR  - 20200623
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 513
IP  - 4
DP  - 2019 Jun 11
TI  - Dysregulation of humoral immunity in Foxp3 conditional-knockout mice.
PG  - 787-793
LID - S0006-291X(19)30732-6 [pii]
LID - 10.1016/j.bbrc.2019.04.090 [doi]
AB  - Foxp3(+) regulatory T cells (Tregs) are crucial for maintaining tolerance to 
      self-antigens and preventing autoimmune diseases. Loss of Foxp3 expression leads 
      to autoimmunity and disrupts humoral immune responses, including hyperproduction 
      of immunoglobulin E (IgE). Elucidation of how Tregs control antibody production 
      can lead to the development of new therapies for autoimmune and allergic 
      diseases. However, premature death of Foxp3-deficient mice makes it difficult to 
      analyze the roles of Tregs in humoral immunity of adult mice. In this study, we 
      developed Foxp3 conditional-knockout mice (Foxp3(flox)R26(CreERT2)) in which the 
      Foxp3 gene was inducibly deleted by tamoxifen administration. After oral 
      administration of tamoxifen, titers of immunoglobulins, particularly IgG2c and 
      IgE, were increased in Foxp3(flox)R26(CreERT2) mice compared with that in 
      controls. Under these conditions, CD4(+) T cells from Foxp3(flox)R26(CreERT2) 
      mice had increased expression of several activation markers, including inducible 
      costimulator and CD40 ligand, as well as the cytokines interleukin 4 and 
      interferon gamma. In addition, the proportions of T follicular helper (Tfh) cells 
      and germinal center (GC) B cells were increased in Foxp3(flox)R26(CreERT2) mice 
      compared with those in controls. These results indicated that Tregs controlled 
      excessive or pathogenic antibody production by suppressing Tfh cell 
      differentiation and GC formation. Furthermore, these data suggested that 
      Foxp3(flox)R26(CreERT2) mice could be a useful tool for screening therapeutic 
      agents.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Tai, Yuki
AU  - Tai Y
AD  - Laboratory of Pharmaceutical Immunology, Faculty of Pharmaceutical Sciences, 
      Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
FAU - Sakamoto, Kazuki
AU  - Sakamoto K
AD  - Laboratory of Pharmaceutical Immunology, Faculty of Pharmaceutical Sciences, 
      Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
FAU - Takano, Azumi
AU  - Takano A
AD  - Laboratory of Pharmaceutical Immunology, Faculty of Pharmaceutical Sciences, 
      Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
FAU - Haga, Katsura
AU  - Haga K
AD  - Laboratory of Pharmaceutical Immunology, Faculty of Pharmaceutical Sciences, 
      Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
FAU - Harada, Yohsuke
AU  - Harada Y
AD  - Laboratory of Pharmaceutical Immunology, Faculty of Pharmaceutical Sciences, 
      Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. 
      Electronic address: yohsuke@rs.noda.tus.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190415
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Foxp3 protein, mouse)
SB  - IM
MH  - Animals
MH  - Antibody Formation/immunology
MH  - B-Lymphocytes/immunology
MH  - Forkhead Transcription Factors/*deficiency/metabolism
MH  - Gene Deletion
MH  - Germinal Center/immunology
MH  - *Immunity, Humoral
MH  - Lymphocyte Activation/immunology
MH  - Mice, Knockout
MH  - T-Lymphocytes, Helper-Inducer/immunology
OTO - NOTNLM
OT  - Cells
OT  - Germinal center
OT  - Humoral immunity
OT  - Regulatory T cells
OT  - T follicular helper
EDAT- 2019/04/20 06:00
MHDA- 2020/06/24 06:00
CRDT- 2019/04/20 06:00
PHST- 2019/02/06 00:00 [received]
PHST- 2019/04/05 00:00 [revised]
PHST- 2019/04/12 00:00 [accepted]
PHST- 2019/04/20 06:00 [pubmed]
PHST- 2020/06/24 06:00 [medline]
PHST- 2019/04/20 06:00 [entrez]
AID - S0006-291X(19)30732-6 [pii]
AID - 10.1016/j.bbrc.2019.04.090 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2019 Jun 11;513(4):787-793. doi: 
      10.1016/j.bbrc.2019.04.090. Epub 2019 Apr 15.