Increased Indoleamine 2,3-Dioxygenase Levels at the Onset of Sjögren’s Syndrome in SATB1-Conditional Knockout Mice
Abstract
:1. Introduction
2. Results
2.1. Expression of IFN-γ Is Upregulated in the Salivary Gland of SATB1cKO Mice upon Reduction in Saliva Production
2.2. l-Kynurenine Is Detected in the Serum of SATB1cKO Mice as Early as Four Weeks after Birth
2.3. IDO Expression Is Induced in SATB1cKO Mice in an IFN-γ-Dependent Manner
3. Discussion
4. Materials and Methods
4.1. Mice
4.2. Flow Cytometry
4.3. RNA Extraction and Real-Time PCR
4.4. Cytokine Assay
4.5. Histopathology and Immunohistochemistry
4.6. Detection of l-Trp and l-KYN in Serum Using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
4.7. In Vivo Neutralization of IFN-γ Functions
4.8. Measurement of Saliva Volume
4.9. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Acknowledgments
Conflicts of Interest
References
- Fox, R.I. Sjogren’s syndrome. Lancet 2005, 366, 321–331. [Google Scholar] [CrossRef]
- Kassan, S.S.; Moutsopoulos, H.M. Clinical manifestations and early diagnosis of Sjogren syndrome. Arch. Intern. Med. 2004, 164, 1275–1284. [Google Scholar] [CrossRef] [PubMed]
- Ramos-Casals, M.; Brito-Zeron, P.; Bombardieri, S.; Bootsma, H.; De Vita, S.; Dorner, T.; Fisher, B.A.; Gottenberg, J.E.; Hernandez-Molina, G.; Kocher, A.; et al. EULAR recommendations for the management of Sjogren’s syndrome with topical and systemic therapies. Ann. Rheum. Dis. 2020, 79, 3–18. [Google Scholar] [CrossRef] [Green Version]
- Dickinson, L.A.; Joh, T.; Kohwi, Y.; Kohwi-Shigematsu, T. A tissue-specific MAR/SAR DNA-binding protein with unusual binding site recognition. Cell 1992, 70, 631–645. [Google Scholar] [CrossRef]
- Cai, S.; Lee, C.C.; Kohwi-Shigematsu, T. SATB1 packages densely looped, transcriptionally active chromatin for coordinated expression of cytokine genes. Nat. Genet. 2006, 38, 1278–1288. [Google Scholar] [CrossRef] [PubMed]
- Will, B.; Vogler, T.O.; Bartholdy, B.; Garrett-Bakelman, F.; Mayer, J.; Barreyro, L.; Pandolfi, A.; Todorova, T.I.; Okoye-Okafor, U.C.; Stanley, R.F.; et al. Satb1 regulates the self-renewal of hematopoietic stem cells by promoting quiescence and repressing differentiation commitment. Nat. Immunol. 2013, 14, 437–445. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Doi, Y.; Yokota, T.; Satoh, Y.; Okuzaki, D.; Tokunaga, M.; Ishibashi, T.; Sudo, T.; Ueda, T.; Shingai, Y.; Ichii, M.; et al. Variable SATB1 Levels Regulate Hematopoietic Stem Cell Heterogeneity with Distinct Lineage Fate. Cell Rep. 2018, 23, 3223–3235. [Google Scholar] [CrossRef]
- Tesone, A.J.; Rutkowski, M.R.; Brencicova, E.; Svoronos, N.; Perales-Puchalt, A.; Stephen, T.L.; Allegrezza, M.J.; Payne, K.K.; Nguyen, J.M.; Wickramasinghe, J.; et al. Satb1 Overexpression Drives Tumor-Promoting Activities in Cancer-Associated Dendritic Cells. Cell Rep. 2016, 14, 1774–1786. [Google Scholar] [CrossRef] [Green Version]
- Satoh, Y.; Yokota, T.; Sudo, T.; Kondo, M.; Lai, A.; Kincade, P.W.; Kouro, T.; Iida, R.; Kokame, K.; Miyata, T.; et al. The Satb1 protein directs hematopoietic stem cell differentiation toward lymphoid lineages. Immunity 2013, 38, 1105–1115. [Google Scholar] [CrossRef] [Green Version]
- Alvarez, J.D.; Yasui, D.H.; Niida, H.; Joh, T.; Loh, D.Y.; Kohwi-Shigematsu, T. The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development. Genes Dev. 2000, 14, 521–535. [Google Scholar]
- Kondo, M.; Tanaka, Y.; Kuwabara, T.; Naito, T.; Kohwi-Shigematsu, T.; Watanabe, A. SATB1 Plays a Critical Role in Establishment of Immune Tolerance. J. Immunol. 2016, 196, 563–572. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Klein, L.; Kyewski, B.; Allen, P.M.; Hogquist, K.A. Positive and negative selection of the T cell repertoire: What thymocytes see (and don’t see). Nat. Rev. Immunol. 2014, 14, 377–391. [Google Scholar] [CrossRef] [Green Version]
- Kitagawa, Y.; Ohkura, N.; Kidani, Y.; Vandenbon, A.; Hirota, K.; Kawakami, R.; Yasuda, K.; Motooka, D.; Nakamura, S.; Kondo, M.; et al. Guidance of regulatory T cell development by Satb1-dependent super-enhancer establishment. Nat. Immunol. 2017, 18, 173–183. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kakugawa, K.; Kojo, S.; Tanaka, H.; Seo, W.; Endo, T.A.; Kitagawa, Y.; Muroi, S.; Tenno, M.; Yasmin, N.; Kohwi, Y.; et al. Essential Roles of SATB1 in Specifying T Lymphocyte Subsets. Cell Rep. 2017, 19, 1176–1188. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schwartz, R.H. Historical overview of immunological tolerance. Cold Spring Harb Perspect. Biol. 2012, 4, a006908. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tanaka, Y.; Sotome, T.; Inoue, A.; Mukozu, T.; Kuwabara, T.; Mikami, T.; Kowhi-Shigematsu, T.; Kondo, M. SATB1 Conditional Knockout Results in Sjogren’s Syndrome in Mice. J. Immunol. 2017, 199, 4016–4022. [Google Scholar] [CrossRef]
- Munn, D.H.; Mellor, A.L. IDO in the Tumor Microenvironment: Inflammation, Counter-Regulation, and Tolerance. Trends Immunol. 2016, 37, 193–207. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yoshida, R.; Imanishi, J.; Oku, T.; Kishida, T.; Hayaishi, O. Induction of pulmonary indoleamine 2,3-dioxygenase by interferon. Proc. Natl. Acad. Sci. USA 1981, 78, 129–132. [Google Scholar] [CrossRef] [Green Version]
- Kang, E.H.; Lee, Y.J.; Hyon, J.Y.; Yun, P.Y.; Song, Y.W. Salivary cytokine profiles in primary Sjogren’s syndrome differ from those in non-Sjogren sicca in terms of TNF-alpha levels and Th-1/Th-2 ratios. Clin. Exp. Rheumatol. 2011, 29, 970–976. [Google Scholar]
- Van Woerkom, J.M.; Kruize, A.A.; Wenting-van Wijk, M.J.; Knol, E.; Bihari, I.C.; Jacobs, J.W.; Bijlsma, J.W.; Lafeber, F.P.; van Roon, J.A. Salivary gland and peripheral blood T helper 1 and 2 cell activity in Sjogren’s syndrome compared with non-Sjogren’s sicca syndrome. Ann. Rheum. Dis. 2005, 64, 1474–1479. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cha, S.; Brayer, J.; Gao, J.; Brown, V.; Killedar, S.; Yasunari, U.; Peck, A.B. A dual role for interferon-gamma in the pathogenesis of Sjogren’s syndrome-like autoimmune exocrinopathy in the nonobese diabetic mouse. Scand. J. Immunol. 2004, 60, 552–565. [Google Scholar] [CrossRef] [PubMed]
- Jaronen, M.; Quintana, F.J. Immunological Relevance of the Coevolution of IDO1 and AHR. Front. Immunol. 2014, 5, 521. [Google Scholar] [CrossRef] [Green Version]
- Parisis, D.; Chivasso, C.; Perret, J.; Soyfoo, M.S.; Delporte, C. Current State of Knowledge on Primary Sjogren’s Syndrome, an Autoimmune Exocrinopathy. J. Clin. Med. 2020, 9, 2299. [Google Scholar] [CrossRef] [PubMed]
- Byrne, G.I.; Lehmann, L.K.; Kirschbaum, J.G.; Borden, E.C.; Lee, C.M.; Brown, R.R. Induction of tryptophan degradation in vitro and in vivo: A gamma-interferon-stimulated activity. J. Interferon Res. 1986, 6, 389–396. [Google Scholar] [CrossRef]
- Mellor, A.L.; Munn, D.H. Tryptophan catabolism and T-cell tolerance: Immunosuppression by starvation? Immunol. Today 1999, 20, 469–473. [Google Scholar] [CrossRef]
- Dai, W.; Gupta, S.L. Regulation of indoleamine 2,3-dioxygenase gene expression in human fibroblasts by interferon-gamma. Upstream control region discriminates between interferon-gamma and interferon-alpha. J. Biol. Chem. 1990, 265, 19871–19877. [Google Scholar] [CrossRef]
- Kadoya, A.; Tone, S.; Maeda, H.; Minatogawa, Y.; Kido, R. Gene structure of human indoleamine 2,3-dioxygenase. Biochem. Biophys. Res. Commun. 1992, 189, 530–536. [Google Scholar] [CrossRef]
- Villarino, A.V.; Kanno, Y.; O’Shea, J.J. Mechanisms and consequences of Jak-STAT signaling in the immune system. Nat. Immunol. 2017, 18, 374–384. [Google Scholar] [CrossRef]
- Michalska, A.; Blaszczyk, K.; Wesoly, J.; Bluyssen, H.A.R. A Positive Feedback Amplifier Circuit That Regulates Interferon (IFN)-Stimulated Gene Expression and Controls Type I and Type II IFN Responses. Front. Immunol. 2018, 9, 1135. [Google Scholar] [CrossRef] [Green Version]
- Jiang, G.M.; Wang, H.S.; Du, J.; Ma, W.F.; Wang, H.; Qiu, Y.; Zhang, Q.G.; Xu, W.; Liu, H.F.; Liang, J.P. Bortezomib Relieves Immune Tolerance in Nasopharyngeal Carcinoma via STAT1 Suppression and Indoleamine 2,3-Dioxygenase Downregulation. Cancer Immunol. Res. 2017, 5, 42–51. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhou, J.; Jin, J.O.; Kawai, T.; Yu, Q. Endogenous programmed death ligand-1 restrains the development and onset of Sjgren’s syndrome in non-obese diabetic mice. Sci. Rep. 2016, 6, 39105. [Google Scholar] [CrossRef] [Green Version]
- Vitali, C.; Bombardieri, S.; Jonsson, R.; Moutsopoulos, H.M.; Alexander, E.L.; Carsons, S.E.; Daniels, T.E.; Fox, P.C.; Fox, R.I.; Kassan, S.S.; et al. Classification criteria for Sjogren’s syndrome: A revised version of the European criteria proposed by the American-European Consensus Group. Ann. Rheum. Dis. 2002, 61, 554–558. [Google Scholar] [CrossRef] [Green Version]
- Shiboski, S.C.; Shiboski, C.H.; Criswell, L.; Baer, A.; Challacombe, S.; Lanfranchi, H.; Schiodt, M.; Umehara, H.; Vivino, F.; Zhao, Y.; et al. American College of Rheumatology classification criteria for Sjogren’s syndrome: A data-driven, expert consensus approach in the Sjogren’s International Collaborative Clinical Alliance cohort. Arthritis Care Res. (Hoboken) 2012, 64, 475–487. [Google Scholar] [CrossRef]
- Shiboski, C.H.; Shiboski, S.C.; Seror, R.; Criswell, L.A.; Labetoulle, M.; Lietman, T.M.; Rasmussen, A.; Scofield, H.; Vitali, C.; Bowman, S.J.; et al. 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjogren’s syndrome: A consensus and data-driven methodology involving three international patient cohorts. Ann. Rheum. Dis. 2017, 76, 9–16. [Google Scholar] [CrossRef] [PubMed]
- Pertovaara, M.; Raitala, A.; Uusitalo, H.; Pukander, J.; Helin, H.; Oja, S.S.; Hurme, M. Mechanisms dependent on tryptophan catabolism regulate immune responses in primary Sjogren’s syndrome. Clin. Exp. Immunol. 2005, 142, 155–161. [Google Scholar] [CrossRef] [PubMed]
- Maria, N.I.; van Helden-Meeuwsen, C.G.; Brkic, Z.; Paulissen, S.M.; Steenwijk, E.C.; Dalm, V.A.; van Daele, P.L.; Martin van Hagen, P.; Kroese, F.G.; van Roon, J.A.; et al. Association of Increased Treg Cell Levels With Elevated Indoleamine 2,3-Dioxygenase Activity and an Imbalanced Kynurenine Pathway in Interferon-Positive Primary Sjogren’s Syndrome. Arthritis Rheumatol. 2016, 68, 1688–1699. [Google Scholar] [CrossRef] [PubMed]
- Skowronska-Krawczyk, D.; Ma, Q.; Schwartz, M.; Scully, K.; Li, W.; Liu, Z.; Taylor, H.; Tollkuhn, J.; Ohgi, K.A.; Notani, D.; et al. Required enhancer-matrin-3 network interactions for a homeodomain transcription program. Nature 2014, 514, 257–261. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- De Boer, J.; Williams, A.; Skavdis, G.; Harker, N.; Coles, M.; Tolaini, M.; Norton, T.; Williams, K.; Roderick, K.; Potocnik, A.J.; et al. Transgenic mice with hematopoietic and lymphoid specific expression of Cre. Eur. J. Immunol. 2003, 33, 314–325. [Google Scholar] [CrossRef]
- Takahashi, S.; Iizuka, H.; Kuwabara, R.; Naito, Y.; Sakamoto, T.; Miyagi, A.; Onozato, M.; Ichiba, H.; Fukushima, T. Determination of l-tryptophan and l-kynurenine derivatized with (R)-4-(3-isothiocyanatopyrrolidin-1-yl)-7-(N,N-dimethylaminosulfonyl)-2,1,3-benzo xadiazole by LC-MS/MS on a triazole-bonded column and their quantification in human serum. Biomed. Chromatogr. 2016, 30, 1481–1486. [Google Scholar] [CrossRef]
- Iizuka, H.; Harashima, T.; Takahashi, S.; Kuwabara, R.; Naito, Y.; Sakamoto, T.; Onozato, M.; Ichiba, H.; Fukushima, T. Chromatographic profiles of tryptophan and kynurenine enantiomers derivatized with (S)-4-(3-isothiocyanatopyrrolidin-1-yl)-7-(N,N-dimethylaminosulfonyl)-2,1,3-benzo xadiazole using LC-MS/MS on a triazole-bonded column. Chirality 2017, 29, 603–609. [Google Scholar] [CrossRef] [PubMed]
- Glasner, A.; Levi, A.; Enk, J.; Isaacson, B.; Viukov, S.; Orlanski, S.; Scope, A.; Neuman, T.; Enk, C.D.; Hanna, J.H.; et al. NKp46 Receptor-Mediated Interferon-gamma Production by Natural Killer Cells Increases Fibronectin 1 to Alter Tumor Architecture and Control Metastasis. Immunity 2018, 48, 396–398. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Tanaka, Y.; Onozato, M.; Mikami, T.; Kohwi-Shigematsu, T.; Fukushima, T.; Kondo, M. Increased Indoleamine 2,3-Dioxygenase Levels at the Onset of Sjögren’s Syndrome in SATB1-Conditional Knockout Mice. Int. J. Mol. Sci. 2021, 22, 10125. https://doi.org/10.3390/ijms221810125
Tanaka Y, Onozato M, Mikami T, Kohwi-Shigematsu T, Fukushima T, Kondo M. Increased Indoleamine 2,3-Dioxygenase Levels at the Onset of Sjögren’s Syndrome in SATB1-Conditional Knockout Mice. International Journal of Molecular Sciences. 2021; 22(18):10125. https://doi.org/10.3390/ijms221810125
Chicago/Turabian StyleTanaka, Yuriko, Mayu Onozato, Tetuo Mikami, Terumi Kohwi-Shigematsu, Takeshi Fukushima, and Motonari Kondo. 2021. "Increased Indoleamine 2,3-Dioxygenase Levels at the Onset of Sjögren’s Syndrome in SATB1-Conditional Knockout Mice" International Journal of Molecular Sciences 22, no. 18: 10125. https://doi.org/10.3390/ijms221810125