Lessons from Animal Models in Sjögren’s Syndrome
Abstract
:1. Introduction
2. Animal Models in Sjögren’s Syndrome Pathogenesis Studies
2.1. Dysregulated Homeostasis in Exocrine Glands
2.2. Dysregulated Homeostasis in the Immune System
3. Insights on Microbiota in Sjögren’s Syndrome from Animal Models
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Goules, A.V.; Tzioufas, A.G. Primary Sjögren’s syndrome: Clinical phenotypes, outcome and the development of biomarkers. Immunol. Res. 2017, 65, 331–344. [Google Scholar] [CrossRef] [PubMed]
- Mariette, X.; Criswell, L.A. Primary Sjogren’s syndrome. N. Engl. J. Med. 2018, 378, 931–939. [Google Scholar] [CrossRef] [PubMed]
- Goules, A.V.; Argyropoulou, O.D.; Pezoulas, V.C.; Chatzis, L.; Critselis, E.; Gandolfo, S.; Ferro, F.; Binutti, M.; Donati, V.; Callgher, S.Z.; et al. Primary Sjögren’s Syndrome of Early and Late Onset: Distinct Clinical Phenotypes and Lymphoma Development. Front. Immunol. 2020, 11, 594096. [Google Scholar] [CrossRef] [PubMed]
- Baldini, C.; Pepe, P.; Quartuccio, L.; Priori, R.; Bartoloni, E.; Alunno, A.; Gattamelata, A.; Maset, M.; Modesti, M.; Tavoni, A.; et al. Primary Sjogren’s syndrome as a multi-organ disease: Impact of the serological profile on the clinical presentation of the disease in a large cohort of Italian patients. Rheumatology 2014, 53, 839–844. [Google Scholar] [CrossRef]
- Cornec, D.; Chiche, L. Is primary Sjögren’s syndrome an orphan disease? A critical appraisal of prevalence studies in Europe. Ann. Rheum. Dis. 2015, 74, e25. [Google Scholar] [CrossRef]
- Maldini, C.; Sero, R.; Fain, O.; Dhote, R.; Amoura, Z.; De Bandt, M.; Delassus, J.L.; Falgarone, G.; Guillevin, L.; Le Guern, V.; et al. Epidemiology of primary Sjogren’s syndrome in a French multiracial/multiethnic area. Arthritis. Care. Res. 2014, 66, 454–463. [Google Scholar] [CrossRef]
- Chatzis, L.G.; Goules, A.V.; Tzioufas, A.G. Searching for the “X Factor” in Sjögren’s Syndrome Female Predilection. Clin. Exp. Rheumatol. 2021, 39, S206–S214. [Google Scholar] [CrossRef]
- Brito-Zeron, P.; Acar-Denizli, N.; Zeher, M.; Rasmussen, A.; Seror, R.; Theander, E.; Li, X.; Baldini, C.; Gottenberg, J.E.; Danda, D.; et al. Influence of geolocation and ethnicity on the phenotypic expression of primary Sjogren’s syndrome at diagnosis in 8310 patients: A cross-sectional study from the big data Sjogren project consortium. Ann. Rheum. Dis. 2017, 76, 1042–1050. [Google Scholar] [CrossRef]
- Jonsson, R. Disease mechanisms in Sjögren’s syndrome: What do we know? Scand. J. Immunol. 2022, 95, e13145. [Google Scholar] [CrossRef]
- Wei, W.; Ahmad, S.S.; Chi, S.; Xie, Y.; Kama, M.A.; Li, J. From molecular mechanism to the etiology of Sjogren syndrome. Curr. Pharm. Des. 2018, 24, 4177–4185. [Google Scholar] [CrossRef]
- Chivasso, C.; Sarrand, J.; Perret, J.; Delporte, C.; Soyfoo, M.S. The involvement of innate and adaptive immunity in the initiation and perpetuation of Sjogren’s syndrome. Int. J. Mol. Sci. 2021, 22, 658. [Google Scholar] [CrossRef] [PubMed]
- Shimizu, T.; Nakamura, H.; Kawakami, A. Role of the innate immunity signaling pathway in the pathogenesis of Sjogren’s syndrome. Int. J. Mol. Sci. 2021, 22, 3090. [Google Scholar] [CrossRef]
- Souyris, M.; Cenac, C.; Azar, P.; Daviaud, D.; Canivet, A.; Grunenwald, S.; Pienkowski, C.; Chaumeil, J.; Mejía, J.E.; Guéry, J.C. TLR7 escapes X chromosome inactivation in immune cells. Sci. Immunol. 2018, 3, eaap8855. [Google Scholar] [CrossRef] [PubMed]
- Goules, A.V.; Kapsogeorgou, E.K.; Tzioufas, A.G. Insight into pathogenesis of Sjogren’s syndrome: Dissection on autoimmune infiltrates and epithelial cells. Clin. Immunol. 2017, 182, 30–40. [Google Scholar] [CrossRef]
- Damsker, J.M.; Hansen, A.M.; Caspi, R.R. Th1 and Th17 cells: Adversaries and collaborators. Ann. N. Y. Acad. Sci. 2010, 1183, 211–221. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.S.; Tato, C.M.; Joyce-Shaikh, B.; Gulen, M.F.; Cayatte, C.; Chen, Y.; Blumenschein, W.M.; Judo, M.; Ayanoglu, G.; McClanahan, T.K.; et al. Interleukin-23-Independent IL-17 production regulates intestinal epithelial permeability. Immunity 2015, 43, 727–738. [Google Scholar] [CrossRef]
- Imgenberg-Kreuz, J.; Rasmussen, A.; Sivils, K.; Nordmark, G. Genetics and epigenetics in primary Sjögren’s syndrome. Rheumatology 2021, 60, 2085–2098. [Google Scholar] [CrossRef]
- Tian, Y.; Yang, H.; Liu, N.; Li, Y.; Chen, J. Advances in Pathogenesis of Sjögren’s Syndrome. J. Immunol. Res. 2021, 2021, 5928232. [Google Scholar] [CrossRef]
- Cruz, A.D.; Kartha, V.; Tilston-Lunel, A.; Mi, R.; Reynolds, T.L.; Mingueneau, M.; Monti, S.; Jensen, J.L.; Skarstein, K.; Varelas, X.; et al. Gene expression alterations in salivary gland epithelia of Sjogren’s syndrome patients are associated with clinical and histopathological manifestations. Sci. Rep. 2021, 11, 11154. [Google Scholar] [CrossRef]
- Asam, S.; Neag, G.; Berardicurti, O.; Gardner, D.; Barone, F. The role of stroma and epithelial cells in primary Sjögren’s syndrome. Rheumatology 2021, 60, 3503–3512. [Google Scholar] [CrossRef]
- Kapsogeorgou, E.K.; Tzioufas, A.G. Interaction of human salivary gland epithelial cells with B lymphocytes: Implications in the pathogenesis of Sjögren’s syndrome. Mediterr. J. Rheumatol. 2020, 31, 424–426. [Google Scholar] [CrossRef]
- Hayashi, T. Dysfunction of lacrimal and salivary glands in Sjogren’s syndrome: Nonimmunologic injury in preinflammatory phase and mouse model. J. Biomed. Biotechnol. 2011, 2011, 407031. [Google Scholar] [CrossRef]
- Nguyen, C.Q.; Sharma, A.; Lee, B.H.; She, J.X.; McIndoe, R.A.; Peck, A.B. Differential gene expression in the salivary gland during development and onset of xerostomia in Sjogren’s syndrome-like disease of the C57BL/6.NODAec1Aec2 mouse. Arthritis. Res. Ther. 2009, 11, R56. [Google Scholar] [CrossRef]
- Killedar, S.Y.; Eckenrode, S.E.; McIndoe, R.A.; She, J.; Nguyen, C.Q.; Peck, A.B.; Cha, S.R. Early pathogenic events associated with Sjogren’s syndrome (SjS)-like disease of the NOD mouse using microarray analysis. Lab. Investig. 2006, 86, 1243–1260. [Google Scholar] [CrossRef]
- Ishimaru, N.; Yoneda, T.; Saegusa, K.; Yanagi, K.; Haneji, N.; Moriyama, K.; Saito, I.; Hayashi, Y. Severe destructive autoimmune lesions with aging in murine Sjogren’s syndrome through fas-mediated apoptosis. Am. J. Pathol. 2000, 156, 1557–1564. [Google Scholar] [CrossRef] [PubMed]
- Shim, G.J.; Warner, M.; Kim, H.J.; Andersson, S.; Liu, L.; Ekman, J.; Imamov, O.; Jones, M.E.; Simpson, E.R.; Gustafsson, J.A. Aromatase deficient mice spontaneously develop a lymphoproliferative autoimmune disease resembling Sjogren’s syndrome. Proc. Natl. Acad. Sci. USA 2004, 101, 12628–12633. [Google Scholar] [CrossRef] [PubMed]
- Ishimaru, N.; Arakaki, R.; Yoshida, S.; Yamada, A.; Noji, S.; Hayashi, Y. Expression of the retinoblastoma protein RbAp48 in exocrine glands leads to Sjogren’s syndrome-like autoimmune exocrinopathy. J. Exp. Med. 2008, 205, 2915–2927. [Google Scholar] [CrossRef] [PubMed]
- Ishimaru, N.; Arakaki, R.; Watanabe, M.; Kobayashi, M.; Miyazaki, K.; Hayashi, Y. Development of autoimmune exocrinopathy resembling Sjögren’s syndrome in estrogen-deficient mice of healthy background. Am. J. Pathol. 2003, 163, 1481–1490. [Google Scholar] [CrossRef] [PubMed]
- Yin, J.; Zheng, J.; Deng, F.; Zhao, W.; Chen, Y.; Huang, Q.; Huang, R.; Wen, L.; Yue, X.; Petersen, F.; et al. Gene expression profiling of lacrimal glands identifies the ectopic expression of mhc ii on glandular cells as a presymptomatic feature in a mouse model of primary Sjogren’s syndrome. Front. Immunol. 2018, 9, 2362. [Google Scholar] [CrossRef]
- Jonsson, R.; Moen, K.; Vestrheim, D.; Szodoray, P. Current issues in Sjogren’s syndrome. Oral. Dis. 2002, 8, 130–140. [Google Scholar] [CrossRef]
- Iizuka, M.; Wakamatsu, E.; Tsuboi, H.; Nakamura, Y.; Hayashi, T.; Matsui, M.; Goto, D.; Ito, S.; Matsumoto, I.; Sumida, T. Pathogenic role of immune response to M3 muscarinic acetylcholine receptor in Sjogren’s syndrome-like sialoadenitis. J. Autoimmun. 2010, 35, 383–389. [Google Scholar] [CrossRef]
- Zheng, J.; Huang, Q.; Huang, R.; Deng, F.; Yue, X.; Yin, J.; Zhao, W.; Chen, Y.; Wen, L.; Zhou, J.; et al. B cells are indispensable for a novel mouse model of primary Sjogren’s syndrome. Front. Immunol. 2017, 8, 1384. [Google Scholar] [CrossRef]
- Soriano-Romani, L.; Contreras-Ruiz, L.; Lopez-Garcia, A.; Diebold, Y.; Masli, S. Topical application of TGF-beta-activating peptide, KRFK, prevents inflammatory manifestations in the TSP-1-deficient mouse model of chronic ocular inflammation. Int. J. Mol. Sci. 2018, 20, 9. [Google Scholar] [CrossRef]
- Xin, X.; Wang, Q.; Qing, J.; Song, W.; Gui, Y.; Li, X.; Li, Y. Th17 cells in primary Sjögren’s syndrome negatively correlate with increased Roseburia and Coprococcus. Front. Immunol. 2022, 13, 974648. [Google Scholar] [CrossRef]
- Jin, L.; Yu, D.; Li, X.; Yu, N.; Wang, Y. CD4+CXCR5+ follicular helper T cells in salivary gland promote B cells maturation in patients with primary Sjogren’s syndrome. Int. J. Clin. Exp. Pathol. 2014, 7, 1988–1996. [Google Scholar] [PubMed]
- Lin, X.; Rui, K.; Deng, J.; Tian, J.; Wang, X.; Wang, S.; Ko, K.H.; Jiao, Z.; Chan, V.S.F.; Lau, C.S.; et al. Th17 cells play a critical role in the development of experimental Sjogren’s syndrome. Ann. Rheum. Dis. 2015, 74, 1302–1310. [Google Scholar] [CrossRef]
- Szabo, K.; Papp, G.; Barath, S.; Gyimesi, E.; Szanto, A.; Zeher, M. Follicular helper T cells may play an important role in the severity of primary Sjogren’s syndrome. Clin. Immunol. 2013, 147, 95–104. [Google Scholar] [CrossRef] [PubMed]
- Johnson, A.C.; Davison, L.M.; Giltiay, N.V.; Vareechon, C.; Li, X.; Jorgensen, T.N. Lack of T cells in Act1-deficient mice results in elevated IgM-specific autoantibodies but reduced lupus-like disease. Eur. J. Immunol. 2012, 42, 1695–1705. [Google Scholar] [CrossRef] [PubMed]
- Contreras Ruiz, L.; Mir, F.A.; Turpie, B.; Masli, S. Thrombospondin-derived peptide attenuates Sjogren’s syndrome-associated ocular surface inflammation in mice. Clin. Exp. Immunol. 2017, 188, 86e95. [Google Scholar] [CrossRef]
- Coursey, T.G.; Bian, F.; Zaheer, M.; Pflugfelder, S.C.; Volpe, E.A.; de Paiva, C.S. Agerelated spontaneous lacrimal keratoconjunctivitis is accompanied by dysfunctional T regulatory cells. Mucosal. Immunol. 2017, 10, 743–756. [Google Scholar] [CrossRef]
- Takada, K.; Takiguchi, M.; Inaba, M. Different effects on the inflammatory lesions in the lacrimal and salivary glands after neonatal thymectomy in IQI/Jic mice, a model for Sjogren’s syndrome. J. Vet. Med. Sci. 2005, 67, 955–957. [Google Scholar] [CrossRef] [PubMed]
- Kramer, J.M. Early events in Sjogren’s syndrome pathogenesis: The importance of innate immunity in disease initiation. Cytokine 2014, 67, 92–101. [Google Scholar] [PubMed]
- Peck, A.B.; Nguyen, C.Q.; Ambrus, J.L. Upregulated chemokine and Rho-GTPase genes define immune cell emigration into salivary glands of Sjögren’s syndrome-susceptible C57BL/6.NOD-Aec1Aec2 mice. Int. J. Mol. Sci. 2021, 22, 7176. [Google Scholar] [CrossRef] [PubMed]
- Nocturne, G.; Mariette, X. Sjögren Syndrome-associated lymphomas: An update on pathogenesis and management. Br. J. Haematol. 2015, 168, 317–327. [Google Scholar] [CrossRef]
- Gao, Y.; Chen, Y.; Zhang, Z.; Yu, X.; Zheng, J. Recent advances in mouse models of Sjögren’s syndrome. Front. Immunol. 2020, 11, 1158. [Google Scholar] [CrossRef]
- Crupi, R.; Cambiaghi, M.; Deckelbaum, R.; Hansen, I.; Mindes, J.; Spina, E.; Battaglia, F. N-3 fatty acids prevent impairment of neurogenesis and synaptic plasticity in B-cell activating factor (BAFF) transgenic mice. Prev. Med. 2012, 54, S103–S108. [Google Scholar]
- Robinson, C.P.; Brayer, J.; Yamachika, S.; Esch, T.R.; Peck, A.B.; Stewart, C.A.; Penn, E.; Jonsson, R.; Humphreys-Beher, M.G. Transfer of human serum IgG to nonobese diabetic Igmu null mice reveals a role for autoantibodies in the loss of secretory function of exocrine tissues in Sjögren’s syndrome. Proc. Natl. Acad. Sci. USA 1998, 95, 7538–7543. [Google Scholar] [CrossRef]
- Ye, L.H.; Shi, H.; Wu, S.; Yu, C.; Wang, B.; Zheng, L. Dysregulated interleukin 11 in primary Sjögren’s syndrome contributes to apoptosis of glandular epithelial cells. Cell Biol. Int. 2020, 44, 327–335. [Google Scholar] [CrossRef]
- Zhou, P.; Chen, J.; He, J.; Zheng, T.; Yunis, J.; Makota, V.; Alexandre, Y.O.; Gong, F.; Zhang, X.; Xie, W.; et al. Low-dose IL-2 therapy invigorates CD8+ T cells for viral control in systemic lupus erythematosus. PLoS Pathog. 2021, 17, e1009858. [Google Scholar] [CrossRef]
- Zhang, C.J.; Wang, C.; Jiang, M.; Gu, C.; Xiao, J.; Chen, X.; Martin, B.N.; Tang, F.; Yamamoto, E.; Xian, Y.; et al. Act1 is a negative regulator in T and B cells via direct inhibition of STAT3. Nat. Commun. 2018, 9, 2745. [Google Scholar] [CrossRef]
- Iizuka, M.; Tsuboi, H.; Matsuo, N.; Asashima, H.; Hirota, T.; Kondo, Y.; Iwakura, Y.; Takahashi, S.; Matsumoto, I.; Sumida, T. A crucial role of RORγt in the development of spontaneous sialadenitis-like Sjögren’s syndrome. J. Immunol. 2015, 194, 56–67. [Google Scholar] [CrossRef]
- Limaye, A.; Hall, B.E.; Zhang, L.; Cho, A.; Prochazkova, M.; Zheng, C.; Walker, M.; Adewusi, F.; Burbelo, P.D.; Sun, Z.J.; et al. Targeted TNF-α overexpression drives salivary gland inflammation. J. Dent. Res. 2019, 98, 713–719. [Google Scholar] [CrossRef]
- Sjöstrand, M.; Johansson, A.; Aqrawi, L.; Olsson, T.; Wahren Herlenius, M.; Espinosa, A. The expression of BAFF is controlled by IRF transcription factors. J. Immunol. 2016, 196, 91–96. [Google Scholar] [CrossRef]
- Mavragani, C.P.; Crow, M.K. Activation of the type I interferon pathway in primary Sjogren’s syndrome. J. Autoimm. 2010, 35, 225–231. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.; Lee, S.; Kwok, K.; Baek, S.Y.; Jang, S.G.; Hong, S.M.; Min, J.W.; Choi, S.S.; Lee, J.; Cho, M.L.; et al. JAK-1 inhibition suppresses interferon-induced BAFF production in human salivary gland. Arthr. Rheum. 2018, 70, 2057–2066. [Google Scholar] [CrossRef] [PubMed]
- Gandolfo, S.; Ciccia, F. JAK/STAT pathway targeting in primary Sjögren syndrome. Rheum. Immunol. Res. 2022, 3, 95–102. [Google Scholar] [CrossRef] [PubMed]
- Aota, K.; Yamanoi, T.; Kani, K.; Ono, S.; Momota, Y.; Azuma, M. Inhibition of JAK-STAT signaling by baricitinib reduces interferon-γ-induced CXCL10 production in human salivary gland ductal cells. Inflammation 2021, 44, 206–216. [Google Scholar] [CrossRef]
- Kiripolsky, J.; Shen, L.; Liang, Y.; Li, A.; Suresh, L.; Lian, Y.; Li, Q.; Gaile, D.P.; Kramer, J.M. Systemic manifestations of primary Sjögren’s syndrome in the NOD.B10Sn-H2(b)/J mouse model. Clin. Immunol. 2017, 183, 225–232. [Google Scholar] [CrossRef]
- Husain-Krautter, S.; Kramer, J.M.; Li, W.; Guo, B.; Rothstein, T.L. The osteopontin transgenic mouse is a new model for Sjogren’s syndrome. Clin. Immun. 2015, 157, 30–42. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.H.; Zhao, M.S.; Zhao, Y. Expression of osteopontin in labial glands of patients with primary Sjögren’s syndrome. Beijing Da Xue Xue Bao Yi Xue Ban 2012, 44, 236–239. [Google Scholar]
- Iwasa, A.; Arakaki, R.; Honma, N.; Ushio, A.; Yamada, A.; Kondo, T.; Kurosawa, E.; Kujiraoka, S.; Tsunematsu, T.; Kudo, Y.; et al. Aromatase controls Sjögren syndrome-like lesions through monocyte chemotactic protein-1 in target organ and adipose tissue associated macrophages. Am. J. Pathol. 2015, 185, 151–161. [Google Scholar] [CrossRef]
- Darabab, R.; Suzuki, T.; Richards, S.M.; Jakobiec, F.A.; Zakka, F.R.; Barabino, S.; Sullivan, D.A. Does estrogen deficiency cause lacrimal gland inflammation and aqueousdeficient dry eye in mice? Exp. Eye Res. 2014, 127, 153–160. [Google Scholar]
- Wang, Y.; Roussel-Queval, A.; Chasson, L.; Kazazian, N.H.; Marcadet, L.; Nezos, A.; Sieweke, M.H.; Mavragani, C.; Alexopoulou, L. TLR7 signaling drives the development of Sjögren’s syndrome. Front. Immun. 2021, 12, 676010. [Google Scholar] [CrossRef]
- Lolmède, K.; Zakaroff-Girard, A.; Dray, C.; Renoud, M.L.; Daviaud, D.; Burcelin, R.; Lafontan, M.; Galitzky, J.; Bouloumié, A. Interrelationship between lymphocytes and leptin in fat depots of obese mice revealed by changes in nutritional status. J. Physiol. Biochem. 2015, 71, 497–507. [Google Scholar] [CrossRef]
- Erbasan, F.; Alikanoğlu, A.S.; Yazısız, V.; Karasu, U.; Balkarlı, A.; Sezer, C.; Terzioglu, M.E. Leptin and leptin receptors in salivary glands of primary Sjogren’s syndrome. Pathol. Res. Pract. 2016, 212, 1010–1014. [Google Scholar] [CrossRef] [PubMed]
- Xu, T.; Xie, W.; Ma, Y.; Zhou, S.; Zhang, L.; Chen, J.; Cai, M.; Sun, R.; Zhang, P.; Yu, S.; et al. Leptin/OB-R signaling is elevated in mice with Sjogren’s syndrome and is implicated in disease pathogenesis. Biochem. Biophys. Res. Commun. 2017, 482, 835–842. [Google Scholar] [CrossRef] [PubMed]
- Stepp, M.A.; Pal-Ghosh, S.; Tadvalkar, G.; Williams, A.; Pflugfelder, S.; de Paiva, C. Reduced corneal innervation in the CD25 null model of Sjögren syndrome. Int. J. Mech. Sci. 2018, 19, 3821. [Google Scholar] [CrossRef]
- Negrini, S.; Emmi, G.; Greco, M.; Borro, M.; Sardanelli, F.; Murdaca, G.; Indiveri, F.; Pupo, F. Sjögren’s syndrome: A systemic autoimmune disease. Clin. Exp. Med. 2022, 22, 9–25. [Google Scholar] [CrossRef]
- Brown, S.D.; Wurst, W.; Kuhn, R.; Hancock, J.M. The functional annotation of mammalian genomes: The challenge of phenotyping. Annu. Rev. Genet. 2009, 43, 305–333. [Google Scholar] [CrossRef]
- Abughanam, G.; Maria, O.M.; Tran, S.D. Studying Sjögren’s syndrome in mice: What is the best available model? J. Oral. Biol. Craniofac. Res. 2021, 11, 245–255. [Google Scholar] [CrossRef] [PubMed]
- Yang, Y.; Xu, J.; Ge, S.; Lai, L. CRISPR/Cas: Advances, limitations, and applications for precision cancer research. Front. Med. 2021, 8, 649896. [Google Scholar] [CrossRef]
- Young, N.A.; Wu, L.C.; Bruss, M.; Kaffenberger, B.H.; Hampton, J.; Bolon, B.; Jarjour, W.N. A chimeric human-mouse model of Sjögren’s syndrome. Clin. Immunol. 2015, 156, 1–8. [Google Scholar] [CrossRef] [PubMed]
- Hou, K.; Wu, Z.; Chen, X.; Wang, J.; Zhang, D.; Xiao, C.; Zhu, D.; Koya, J.B.; Wei, L.; Li, J.; et al. Microbiota in health and diseases. Signal Transduct. Target. Ther. 2022, 7, 135. [Google Scholar] [CrossRef] [PubMed]
- De Luca, F.; Shoenfeld, Y. The microbiome in autoimmune diseases. Clin. Exp. Immunol. 2019, 195, 74–85. [Google Scholar] [CrossRef]
- Berg, G.; Rybakova, D.; Fischer, D.; Cernava, T.; Vergès, M.C.; Charles, T.; Chen, X.; Cocolin, L.; Eversole, K.; Corral, G.H.; et al. Microbiome definition re-visited: Old concepts and new challenges. Microbiome 2020, 8, 103. [Google Scholar] [CrossRef]
- Manasson, J.; Blank, R.B.; Scher, J.U. The microbiome in rheumatology: Where are we and where should we go? Ann. Rheum. Dis. 2020, 79, 727–733. [Google Scholar] [CrossRef] [PubMed]
- Yao, Y.F.; Wang, M.Y.; Dou, X.X. Gastrointestinal microbiome and primary Sjögren’s syndrome: A review of the literature and conclusions. Int. J. Ophthalmol. 2022, 15, 1864–1872. [Google Scholar] [CrossRef] [PubMed]
- Cao, Y.; Lu, H.; Xu, W.; Zhong, M. Gut microbiota and Sjögren’s syndrome: A two-sample Mendelian randomization study. Front. Immunol. 2023, 14, 1187906. [Google Scholar] [CrossRef]
- Skelly, A.N.; Sato, Y.; Kearney, S.; Honda, K. Mining the microbiota for microbial and metabolite-based immunotherapies. Nat. Rev. Immunol. 2019, 19, 305–323. [Google Scholar] [CrossRef]
- Bach, J.F. The hygiene hypothesis in autoimmunity: The role of pathogens and commensals. Nat. Rev. Immunol. 2018, 18, 105–120. [Google Scholar] [CrossRef]
- Cano-Ortiz, A.; Laborda-Illanes, A.; Plaza-Andrades, I.; Membrillo Del Pozo, A.; Villarrubia Cuadrado, A.; Rodríguez Calvo de Mora, M.; Leiva-Gea, I.; Sanchez-Alcoholado, L.; Queipo-Ortuño, M.I. Connection between the gut microbiome, systemic inflammation, gut permeability and FOXP3 expression in patients with primary Sjögren’s syndrome. Int. J. Mol. Sci. 2020, 21, E8733. [Google Scholar] [CrossRef] [PubMed]
- Deng, C.; Xiao, Q.; Fei, Y. A glimpse into the microbiome of Sjögren’s syndrome. Front. Immunol. 2022, 13, 918619. [Google Scholar] [CrossRef]
- van der Meulen, T.A.; Harmsen, H.; Bootsma, H.; Spijkervet, F.; Kroese, F.; Vissink, A. The microbiome-systemic diseases connection. Oral. Dis. 2016, 22, 719–734. [Google Scholar] [CrossRef]
- Wang, C.J.; Zaheer, M.; Bian, F.; Quach, D.; Swennes, A.G.; Britton, R.A.; Pflugfelder, S.C.; de Paiva, C.S. Sjögren-like lacrimal keratoconjunctivitis in germ-free mice. Int. J. Mol. Sci. 2018, 19, E565. [Google Scholar] [CrossRef]
- Mölzer, C.; Heissigerova, J.; Wilson, H.M.; Kuffova, L.; Forrester, J.V. Immune privilege: The microbiome and uveitis. Front. Immunol. 2020, 11, 608377. [Google Scholar] [CrossRef] [PubMed]
- Szczerba, B.M.; Kaplonek, P.; Wolska, N.; Podsiadlowska, A.; Rybakowska, P.D.; Dey, P.; Rasmussen, A.; Grundahl, K.; Hefner, K.S.; Stone, D.U.; et al. Interaction between innate immunity and Ro52-induced antibody causes Sjögren’s syndrome-like disorder in mice. Ann. Rheum. Dis. 2016, 75, 617–622. [Google Scholar] [CrossRef]
- Zaheer, M.; Wang, C.J.; Bian, F.; Yu, Z.Y.; Hernandez, H.; de Souza, R.G.; Simmons, K.T.; Schady, D.; Swennes, A.G.; Pflugfelder, S.C.; et al. Protective role of commensal bacteria in Sjögren syndrome. J. Autoimmun. 2018, 93, 45–56. [Google Scholar] [CrossRef]
- Verstappen, G.M.; Corneth, O.B.J.; Bootsma, H.; Kroese, F.G.M. Th17 cells in primary Sjögren’s syndrome: Pathogenicity and plasticity. J. Autoimmun. 2018, 87, 16–25. [Google Scholar] [CrossRef]
- Yanagisawa, N.; Ueshiba, H.; Abe, Y.; Kato, H.; Higuchi, T.; Yagi, J. Outer membrane protein of gut commensal microorganism induces autoantibody production and extra-intestinal gland inflammation in mice. Int. J. Mol. Sci. 2018, 19, 3241. [Google Scholar] [CrossRef]
- Higuchi, T.; Haruta, I.; Shibata, N.; Yanagisawa, N.; Yagi, J. Flagellar filament structural protein induces Sjögren’s syndrome-like sialadenitis in mice. Oral. Dis. 2017, 23, 636–643. [Google Scholar] [CrossRef] [PubMed]
- Postler, T.S.; Ghosh, S. Understanding the holobiont: How microbial metabolites affect human health and shape the immune system. Cell Metab. 2017, 26, 110–130. [Google Scholar] [CrossRef]
- Fakharian, F.; Thirugnanam, S.; Welsh, D.A.; Kim, W.-K.; Rappaport, J.; Bittinger, K.; Rout, N. The Role of Gut Dysbiosis in the Loss of Intestinal Immune Cell Functions and Viral Pathogenesis. Microorganisms 2023, 11, 1849. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.; Choi, S.H.; Kim, Y.J.; Jeong, H.J.; Ryu, J.S.; Lee, H.J.; Kim, T.W.; Im, S.H.; Oh, J.Y.; Kim, M.K. Clinical effect of IRT-5 probiotics on immune modulation of autoimmunity or alloimmunity in the eye. Nutrients 2017, 9, 1166. [Google Scholar] [CrossRef]
- Choi, S.H.; Oh, J.W.; Ryu, J.S.; Kim, H.M.; Im, S.H.; Kim, K.P.; Kim, M.K. IRT5 probiotics changes immune modulatory protein expression in the extraorbital lacrimal glands of an autoimmune dry eye mouse model. Investig. Ophthalmol. Vis. Sci. 2020, 61, 42. [Google Scholar] [CrossRef]
- Bron, A.J.; de Paiva, C.S.; Chauhan, S.K.; Bonini, S.; Gabison, E.E.; Jain, S.; Knop, E.; Markoulli, M.; Ogawa, Y.; Perez, V.; et al. TFOS DEWS II pathophysiology report. Ocul. Surf. 2017, 15, 438–510. [Google Scholar] [PubMed]
- Hori, J.; Yamaguchi, T.; Keino, H.; Hamrah, P.; Maruyama, K. Immune privilege in corneal transplantation. Prog. Retin. Eye Res. 2019, 72, 100758. [Google Scholar] [CrossRef] [PubMed]
Mouse Model | Local Disease | Inflammatory Infiltration | Systemic Disease | Autoantibodies | ||||
---|---|---|---|---|---|---|---|---|
Dry Mouth | Dry Eyes | SG | LG | Anti-SSA/Ro | Anti-SSB/La | |||
Genetic mouse models | NZB/NZW F1 | - | + | + | + | + | - | - |
MRL/lpr (MRL/Mp-lpr) | + | + | + | + | + | + | + | |
NOD NFS/sld | + | + | + | + | + | + | + | |
McH-lpr/lpr-RA1 | + | - | + | + | + | - | - | |
IQI/Jic | - | - | + | + | + | - | - | |
Aly/aly | - | - | + | + | + | - | - | |
Ar-KO | - | - | + | + | + | + | + | |
Id3-KO | + | + | + | + | +/- | + | + | |
T-cell specific PI3K-KO | - | + | - | + | + | + | + | |
Act1-KO | + | + | + | + | + | + | + | |
Aire-KO | - | + | + | + | - | - | - | |
Erdj5-ko | + | - | + | - | - | + | + | |
CD25-KO | - | + | - | + | + | - | - | |
Nfkbiz | - | + | - | + | + | - | - | |
IxBɑ | - | - | + | + | + | + | + | |
RBAp48 Tg | + | + | + | + | - | + | + | |
BAFF Tg | + | - | + | + | + | - | - | |
IL-12 Tg | + | - | + | + | - | - | + | |
IL-14a Tg | - | - | + | - | + | + | + | |
IL-10 Tg | + | + | + | + | - | - | - | |
Opn Tg | + | - | + | + | - | + | - | |
Induced mouse models | Salivary gland protein | + | - | + | - | - | - | - |
M3R | + | - | + | - | - | - | - | |
Ro60 peptide | + | + | + | + | - | + | + | |
Adenovirus 5 | + | - | + | - | - | - | - | |
Murine CMV | + | - | + | + | - | + | + | |
Humanized mouse model | + | - | + | + | - | - | - |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 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
Mieliauskaitė, D.; Kontenis, V.; Šiaurys, A. Lessons from Animal Models in Sjögren’s Syndrome. Int. J. Mol. Sci. 2023, 24, 12995. https://doi.org/10.3390/ijms241612995
Mieliauskaitė D, Kontenis V, Šiaurys A. Lessons from Animal Models in Sjögren’s Syndrome. International Journal of Molecular Sciences. 2023; 24(16):12995. https://doi.org/10.3390/ijms241612995
Chicago/Turabian StyleMieliauskaitė, Diana, Vilius Kontenis, and Almantas Šiaurys. 2023. "Lessons from Animal Models in Sjögren’s Syndrome" International Journal of Molecular Sciences 24, no. 16: 12995. https://doi.org/10.3390/ijms241612995