PMID- 34576286
OWN - NLM
STAT- MEDLINE
DCOM- 20211025
LR  - 20240226
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 18
DP  - 2021 Sep 19
TI  - Increased Indoleamine 2,3-Dioxygenase Levels at the Onset of Sjogren's Syndrome 
      in SATB1-Conditional Knockout Mice.
LID - 10.3390/ijms221810125 [doi]
LID - 10125
AB  - Sjogren's syndrome (SS) is a chronic autoimmune disease characterized by 
      dysfunction of salivary and lacrimal glands, resulting in xerostomia (dry mouth) 
      and keratoconjunctivitis sicca (dry eyes). Autoantibodies, such as anti-SSA and 
      anti-SSB antibodies, are hallmarks and important diagnostic factors for SS. In 
      our previous study, we demonstrated that SS-like xerostomia was observed in SATB1 
      conditional knockout (SATB1cKO) mice, in which the floxed SATB1 gene was 
      specifically deleted in hematopoietic cells as early as 4 weeks of age. In these 
      mice, autoantibodies were not detected until 8 weeks of age in SATB1cKO mice, 
      although exocrine gland function reached its lowest at this age. Therefore, other 
      markers may be necessary for the diagnosis of SS in the early phase. Here, we 
      found that mRNA expression of the interferongamma (IFN-gamma) gene and the IFN-responsive 
      indoleamine 2,3-dioxygenase (IDO) gene is upregulated in the salivary glands of 
      SATB1cKO mice after 3 and 4 weeks of age, respectively. We detected l-kynurenine 
      (l-KYN), an intermediate of l-tryptophan (l-Trp) metabolism mediated by IDO, in 
      the serum of SATB1cKO mice after 4 weeks of age. In addition, the upregulation of 
      IDO expression was significantly suppressed by the administration of IFN-gamma 
      neutralizing antibodies in SATB1cKO mice. These results suggest that the 
      induction of IFN-dependent IDO expression is an initial event that occurs 
      immediately after the onset of SS in SATB1cKO mice. These results also imply that 
      serum l-KYN could be used as a marker for SS diagnosis in the early phases of the 
      disease before autoantibodies are detectable.
FAU - Tanaka, Yuriko
AU  - Tanaka Y
AUID- ORCID: 0000-0002-9278-7677
AD  - Department of Molecular Immunology, Toho University School of Medicine, Tokyo 
      143-8540, Japan.
FAU - Onozato, Mayu
AU  - Onozato M
AD  - Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho 
      University, Chiba 274-8510, Japan.
FAU - Mikami, Tetuo
AU  - Mikami T
AD  - Department of Pathology, Toho University School of Medicine, Tokyo 143-8540, 
      Japan.
FAU - Kohwi-Shigematsu, Terumi
AU  - Kohwi-Shigematsu T
AD  - Department of Orofacial Sciences, University of California San Francisco School 
      of Dentistry, San Francisco, CA 94143, USA.
FAU - Fukushima, Takeshi
AU  - Fukushima T
AUID- ORCID: 0000-0002-6086-4156
AD  - Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho 
      University, Chiba 274-8510, Japan.
FAU - Kondo, Motonari
AU  - Kondo M
AUID- ORCID: 0000-0002-1565-8804
AD  - Department of Molecular Immunology, Toho University School of Medicine, Tokyo 
      143-8540, Japan.
LA  - eng
GR  - JP24390121 to M.K. and Y.T., JP26670240 to M.K., 18K07075 to Y.T./MEXT/JSPS 
      KAKENHI/
GR  - Strategic Research Foundation Grant-aided Project for Private Schools at Heisei 
      26th (S1411015 )/Ministry of Education, Culture, Sports, Science and Technology/
GR  - Research Promotion Grant (14-02)/Toho University Graduate School of Medicine/
GR  - Project Research Grants (23-4 and 26-22 to Y.T.)/Toho University School of 
      Medicine/
GR  - N/A/Public Foundation of the Vaccination Research Center/
GR  - Joint research Fund to M.K., Y.T., M.O. and K.F./Toho University/
GR  - Initiative for Realizing Diversity in the Research Environment/Japan Science and 
      Technology Agency/
GR  - R37CA39681 to T.K.-S./GF/NIH HHS/United States
GR  - Grant-in Aid for Private University Research Branding Project/Ministry of 
      Education, Culture, Sports, Science and Technology/
GR  - Grant for Research Initiative Program/Toho University/
PT  - Journal Article
DEP - 20210919
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Cytokines)
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Matrix Attachment Region Binding Proteins)
RN  - 0 (Satb1 protein, mouse)
RN  - 343-65-7 (Kynurenine)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 8DUH1N11BX (Tryptophan)
SB  - IM
MH  - Animals
MH  - Cytokines/metabolism
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/*metabolism
MH  - Inflammation Mediators/metabolism
MH  - Interferon-gamma/metabolism
MH  - Kynurenine/blood/metabolism
MH  - Matrix Attachment Region Binding Proteins/*deficiency/metabolism
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Saliva/metabolism
MH  - Salivary Glands/metabolism
MH  - Sjogren's Syndrome/blood/*enzymology
MH  - Tryptophan/metabolism
MH  - Up-Regulation
MH  - Mice
PMC - PMC8468825
OTO - NOTNLM
OT  - Sjogren's syndrome
OT  - autoimmunity
OT  - interferon gamma
OT  - tryptophan metabolism
COIS- The authors declare no conflict of interest.
EDAT- 2021/09/29 06:00
MHDA- 2021/10/26 06:00
PMCR- 2021/09/19
CRDT- 2021/09/28 01:19
PHST- 2021/08/15 00:00 [received]
PHST- 2021/09/10 00:00 [revised]
PHST- 2021/09/17 00:00 [accepted]
PHST- 2021/09/28 01:19 [entrez]
PHST- 2021/09/29 06:00 [pubmed]
PHST- 2021/10/26 06:00 [medline]
PHST- 2021/09/19 00:00 [pmc-release]
AID - ijms221810125 [pii]
AID - ijms-22-10125 [pii]
AID - 10.3390/ijms221810125 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Sep 19;22(18):10125. doi: 10.3390/ijms221810125.