PMID- 28804991
OWN - NLM
STAT- MEDLINE
DCOM- 20171106
LR  - 20180119
IS  - 2326-5205 (Electronic)
IS  - 2326-5191 (Linking)
VI  - 69
IP  - 11
DP  - 2017 Nov
TI  - NF-kappaB2 Controls the Migratory Activity of Memory T Cells by Regulating Expression 
      of CXCR4 in a Mouse Model of Sjogren's Syndrome.
PG  - 2193-2202
LID - 10.1002/art.40230 [doi]
AB  - OBJECTIVE: Dysregulated chemokine signaling contributes to autoimmune diseases by 
      facilitating aberrant T cell infiltration into target tissues, but the specific 
      chemokines, receptors, and T cell populations remain largely unidentified. The 
      aim of this study was to examine the role of the potent chemokine CXCL12 and its 
      receptor CXCR4 in the T cell autoimmune response, using alymphoplasia (aly)/aly 
      mice, a model of Sjogren's syndrome (SS). METHODS: T cell phenotypes in the 
      salivary gland of aly/aly mice were evaluated using immunologic analysis. An 
      in vitro migration assay was used to assess T cell migratory activity toward 
      several chemokines. Gene expression of chemokine receptors and transforming 
      growth factor beta receptors (TGFbetaRs) was measured by quantitative reverse 
      transcription-polymerase chain reaction. The CXCR4 antagonist AMD3100 was 
      administered to the aly/aly mice in order to evaluate its suppressive effect on 
      autoimmune lesions. RESULTS: Effector memory T (TEM) cells derived from aly/aly 
      mice demonstrated higher in vitro migratory activity toward CXCL12 than did TEM 
      cells from aly/+ mice. CXCL12 expression was specifically up-regulated in the SS 
      target cells of aly/aly mice. TEM cells from RelB(-/-) mice, but not Nfkb1(-/-) 
      mice, also showed high migratory activity toward CXCL12, implicating a role of 
      the nonclassical RelB/NF-kappaB2 pathway in the regulation of TEM cell migration. TEM 
      cells from aly/aly mice also overexpressed TGFbetaR type I (TGFbetaRI) and TGFbetaRII. The 
      CXCR4 antagonist AMD3100 suppressed autoimmune lesions in aly/aly mice by 
      reducing TEM cell infiltration. CONCLUSION: Our results suggest that the 
      RelB/NF-kappaB2 pathway regulates T cell migration to autoimmune targets through 
      TGFbeta/TGFbetaR-dependent regulation of CXCL12/CXCR4 signaling. This suggests that 
      these signaling pathways are potential therapeutic targets for the treatment of 
      autoimmune diseases.
CI  - (c) 2017, American College of Rheumatology.
FAU - Kurosawa, Mie
AU  - Kurosawa M
AD  - Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
FAU - Arakaki, Rieko
AU  - Arakaki R
AD  - Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
FAU - Yamada, Akiko
AU  - Yamada A
AD  - Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
FAU - Tsunematsu, Takaaki
AU  - Tsunematsu T
AD  - Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
FAU - Kudo, Yasusei
AU  - Kudo Y
AD  - Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
FAU - Sprent, Jonathan
AU  - Sprent J
AD  - Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
FAU - Ishimaru, Naozumi
AU  - Ishimaru N
AD  - Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171017
PL  - United States
TA  - Arthritis Rheumatol
JT  - Arthritis & rheumatology (Hoboken, N.J.)
JID - 101623795
RN  - 0 (CXCR4 protein, mouse)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Cxcl12 protein, mouse)
RN  - 0 (NF-kappa B p52 Subunit)
RN  - 0 (Nfkb2 protein, mouse)
RN  - 0 (Receptors, CXCR4)
RN  - 0 (Relb protein, mouse)
RN  - 147337-75-5 (Transcription Factor RelB)
SB  - IM
MH  - Animals
MH  - Chemokine CXCL12/immunology
MH  - Chemotaxis, Leukocyte/*genetics/immunology
MH  - Disease Models, Animal
MH  - Gene Expression Regulation
MH  - In Vitro Techniques
MH  - Mice
MH  - Mice, Knockout
MH  - NF-kappa B p52 Subunit/*genetics
MH  - Receptors, CXCR4/*genetics/immunology
MH  - Sjogren's Syndrome/*genetics/immunology
MH  - T-Lymphocytes/*immunology
MH  - Transcription Factor RelB/genetics
EDAT- 2017/08/15 06:00
MHDA- 2017/11/07 06:00
CRDT- 2017/08/15 06:00
PHST- 2017/03/07 00:00 [received]
PHST- 2017/08/09 00:00 [accepted]
PHST- 2017/08/15 06:00 [pubmed]
PHST- 2017/11/07 06:00 [medline]
PHST- 2017/08/15 06:00 [entrez]
AID - 10.1002/art.40230 [doi]
PST - ppublish
SO  - Arthritis Rheumatol. 2017 Nov;69(11):2193-2202. doi: 10.1002/art.40230. Epub 2017 
      Oct 17.