PMID- 25548232
OWN - NLM
STAT- MEDLINE
DCOM- 20150414
LR  - 20150117
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 194
IP  - 3
DP  - 2015 Feb 1
TI  - CD26-mediated induction of EGR2 and IL-10 as potential regulatory mechanism for 
      CD26 costimulatory pathway.
PG  - 960-72
LID - 10.4049/jimmunol.1402143 [doi]
AB  - CD26 is associated with T cell signal transduction processes as a costimulatory 
      molecule, and CD26(+) T cells have been suggested to be involved in the 
      pathophysiology of diverse autoimmune diseases. Although the cellular and 
      molecular mechanisms involved in CD26-mediated T cell activation have been 
      extensively evaluated by our group and others, potential negative feedback 
      mechanisms to regulate CD26-mediated activation still remain to be elucidated. In 
      the present study, we examine the expression of inhibitory molecules induced via 
      CD26-mediated costimulation. We show that coengagement of CD3 and CD26 induces 
      preferential production of IL-10 in human CD4(+) T cells, mediated through NFAT 
      and Raf-MEK-ERK pathways. A high level of early growth response 2 (EGR2) is also 
      induced following CD26 costimulation, possibly via NFAT and AP-1-mediated 
      signaling, and knockdown of EGR2 leads to decreased IL-10 production. 
      Furthermore, CD3/CD26-stimulated CD4(+) T cells clearly suppress proliferative 
      activity and effector cytokine production of bystander T cells in an 
      IL-10-dependent manner. Taken together, our data suggest that robust CD26 
      costimulatory signaling induces preferential expression of EGR2 and IL-10 as a 
      potential mechanism for regulating CD26-mediated activation.
CI  - Copyright (c) 2015 by The American Association of Immunologists, Inc.
FAU - Hatano, Ryo
AU  - Hatano R
AD  - Department of Therapy Development and Innovation for Immune Disorders and 
      Cancers, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan; 
      Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, 
      Tokyo 113-8421, Japan; and.
FAU - Ohnuma, Kei
AU  - Ohnuma K
AD  - Department of Therapy Development and Innovation for Immune Disorders and 
      Cancers, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan;
FAU - Otsuka, Haruna
AU  - Otsuka H
AD  - Department of Therapy Development and Innovation for Immune Disorders and 
      Cancers, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan;
FAU - Komiya, Eriko
AU  - Komiya E
AD  - Department of Therapy Development and Innovation for Immune Disorders and 
      Cancers, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan;
FAU - Taki, Izumi
AU  - Taki I
AD  - Department of Therapy Development and Innovation for Immune Disorders and 
      Cancers, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan;
FAU - Iwata, Satoshi
AU  - Iwata S
AD  - Department of Therapy Development and Innovation for Immune Disorders and 
      Cancers, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan;
FAU - Dang, Nam H
AU  - Dang NH
AD  - Division of Hematology/Oncology, University of Florida, Gainesville, FL 32610.
FAU - Okumura, Ko
AU  - Okumura K
AD  - Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, 
      Tokyo 113-8421, Japan; and.
FAU - Morimoto, Chikao
AU  - Morimoto C
AD  - Department of Therapy Development and Innovation for Immune Disorders and 
      Cancers, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan; 
      morimoto@ims.u-tokyo.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141229
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Cytokines)
RN  - 0 (Early Growth Response Protein 2)
RN  - 0 (NFATC Transcription Factors)
RN  - 130068-27-8 (Interleukin-10)
RN  - EC 2.7.11.1 (raf Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.14.5 (Dipeptidyl Peptidase 4)
SB  - IM
MH  - Cytokines/metabolism
MH  - Dipeptidyl Peptidase 4/*metabolism
MH  - Early Growth Response Protein 2/genetics/*metabolism
MH  - Gene Expression
MH  - Humans
MH  - *Immunomodulation
MH  - Immunophenotyping
MH  - Interleukin-10/biosynthesis/*metabolism
MH  - Lymphocyte Activation
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NFATC Transcription Factors/metabolism
MH  - Phenotype
MH  - *Signal Transduction
MH  - T-Lymphocyte Subsets/immunology/metabolism
MH  - T-Lymphocytes, Regulatory/immunology/metabolism
MH  - raf Kinases/metabolism
EDAT- 2014/12/31 06:00
MHDA- 2015/04/15 06:00
CRDT- 2014/12/31 06:00
PHST- 2014/12/31 06:00 [entrez]
PHST- 2014/12/31 06:00 [pubmed]
PHST- 2015/04/15 06:00 [medline]
AID - jimmunol.1402143 [pii]
AID - 10.4049/jimmunol.1402143 [doi]
PST - ppublish
SO  - J Immunol. 2015 Feb 1;194(3):960-72. doi: 10.4049/jimmunol.1402143. Epub 2014 Dec 
      29.