PMID- 37279329
OWN - NLM
STAT- MEDLINE
DCOM- 20230906
LR  - 20230912
IS  - 1460-2377 (Electronic)
IS  - 0953-8178 (Linking)
VI  - 35
IP  - 9
DP  - 2023 Sep 5
TI  - Foxp3 and Bcl6 deficiency synergistically induces spontaneous development of 
      atopic dermatitis-like skin disease.
PG  - 423-435
LID - 10.1093/intimm/dxad018 [doi]
AB  - Atopic dermatitis (AD) is a common chronic skin disease caused by immune 
      dysfunction, specifically the hyperactivation of Th2 immunity. AD is a complex 
      disease with multiple factors contributing to its development; however, the 
      interaction between these factors is not fully understood. In this study, we 
      demonstrated that the conditional deletion of both the forkhead box p3 (Foxp3) 
      and B-cell lymphoma 6 (Bcl6) genes induced the spontaneous development of AD-like 
      skin inflammation with hyperactivation of type 2 immunity, skin barrier 
      dysfunction, and pruritus, which were not induced by the single deletion of each 
      gene. Furthermore, the development of AD-like skin inflammation was largely 
      dependent on IL-4/13 signaling but not on immunoglobulin E (IgE). Interestingly, 
      we found that the loss of Bcl6 alone increased the expression of thymic stromal 
      lymphopoietin (TSLP) and interleukin (IL)-33 in the skin, suggesting that Bcl6 
      controls Th2 responses by suppressing TSLP and IL-33 expression in epithelial 
      cells. Our results suggest that Foxp3 and Bcl6 cooperatively suppress the 
      pathogenesis of AD. Furthermore, these results revealed an unexpected role of 
      Bcl6 in suppressing Th2 responses in the skin.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of The 
      Japanese Society for Immunology. All rights reserved. For permissions, please 
      e-mail: journals.permissions@oup.com.
FAU - Tai, Yuki
AU  - Tai Y
AD  - Laboratory of Pharmaceutical Immunology, Department of Medicinal and Life 
      Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, 
      Chiba 278-8510, Japan.
FAU - Sakaida, Yuki
AU  - Sakaida Y
AD  - Laboratory of Pharmaceutical Immunology, Department of Medicinal and Life 
      Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, 
      Chiba 278-8510, Japan.
FAU - Kawasaki, Riyo
AU  - Kawasaki R
AD  - Laboratory of Pharmaceutical Immunology, Department of Medicinal and Life 
      Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, 
      Chiba 278-8510, Japan.
FAU - Kanemaru, Kaori
AU  - Kanemaru K
AD  - Department of Applied Biological Science, Faculty of Science and Technology, 
      Tokyo University of Science, Noda, Chiba 278-8510, Japan.
FAU - Akimoto, Kazunori
AU  - Akimoto K
AD  - Laboratory of Molecular Medical Science, Department of Medicinal and Life 
      Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, 
      Chiba 278-8510, Japan.
FAU - Brombacher, Frank
AU  - Brombacher F
AD  - Division of Immunology, Health Science Faculty, International Centre for Genetic 
      Engineering and Biotechnology (ICGEB), Cape Town Component & Institute of 
      Infectious Diseases and Molecular Medicine (IDM), University of Cape Town, Cape 
      Town 7701, South Africa.
FAU - Ogawa, Shuhei
AU  - Ogawa S
AD  - Division of Integrated Research, Research Institute for Biomedical Sciences, 
      Tokyo University of Science, Noda, Chiba 278-0022, Japan.
FAU - Nakamura, Yoshikazu
AU  - Nakamura Y
AD  - Department of Applied Biological Science, Faculty of Science and Technology, 
      Tokyo University of Science, Noda, Chiba 278-8510, Japan.
FAU - Harada, Yohsuke
AU  - Harada Y
AUID- ORCID: 0000-0002-8023-1030
AD  - Laboratory of Pharmaceutical Immunology, Department of Medicinal and Life 
      Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, 
      Chiba 278-8510, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Int Immunol
JT  - International immunology
JID - 8916182
RN  - 0 (Cytokines)
RN  - GT0IL38SP4 (Thymic Stromal Lymphopoietin)
SB  - IM
MH  - Humans
MH  - *Dermatitis, Atopic
MH  - Cytokines/metabolism
MH  - Skin
MH  - Pruritus
MH  - Thymic Stromal Lymphopoietin
MH  - Inflammation/metabolism
OTO - NOTNLM
OT  - IL-13
OT  - IL-33
OT  - IL-4
OT  - Th2
OT  - Treg
EDAT- 2023/06/06 19:13
MHDA- 2023/09/06 06:42
CRDT- 2023/06/06 14:32
PHST- 2023/04/12 00:00 [received]
PHST- 2023/05/01 00:00 [accepted]
PHST- 2023/09/06 06:42 [medline]
PHST- 2023/06/06 19:13 [pubmed]
PHST- 2023/06/06 14:32 [entrez]
AID - 7189815 [pii]
AID - 10.1093/intimm/dxad018 [doi]
PST - ppublish
SO  - Int Immunol. 2023 Sep 5;35(9):423-435. doi: 10.1093/intimm/dxad018.