Age-associated B cell infiltration in salivary glands represents a hallmark of Sjögren's-like disease in aging mice.
Age-associated B cells
Aging
Autoimmunity
Mice
Salivary glands
Sjögren’s disease
Journal
GeroScience
ISSN: 2509-2723
Titre abrégé: Geroscience
Pays: Switzerland
ID NLM: 101686284
Informations de publication
Date de publication:
24 Apr 2024
24 Apr 2024
Historique:
received:
23
02
2024
accepted:
09
04
2024
medline:
24
4
2024
pubmed:
24
4
2024
entrez:
24
4
2024
Statut:
aheadofprint
Résumé
Sjögren's disease (SjD), characterized by circulating autoantibodies and exocrine gland inflammation, is typically diagnosed in women over 50 years of age. However, the contribution of age to SjD pathogenesis is unclear. C57BL/6 female mice at different ages were studied to investigate how aging influences the dynamics of salivary gland inflammation. Salivary glands were characterized for immune cell infiltration, inflammatory gene expression, and saliva production. At 8 months, gene expression of several chemokines involved in immune cell trafficking was significantly elevated. At this age, age-associated B cells (ABCs), a unique subset of B cells expressing the myeloid markers CD11b and/or CD11c, were preferentially enriched in the salivary glands compared to other organs like the spleen or liver. The salivary gland ABCs increased with age and positively correlated with increased CD4 T follicular helper cells. By 14 months, lymphocytic foci of well-organized T and B cells spontaneously developed in the salivary glands. In addition, the mice progressively developed high titers of serum autoantibodies. A subset of aged mice developed salivary gland dysfunction mimicking SjD patients. Our data demonstrates that aging is a significant confounding factor for SjD. Thus, aged female C57BL/6 mice are more appropriate and a valuable preclinical model for investigating SjD pathogenesis and novel therapeutic interventions.
Identifiants
pubmed: 38656650
doi: 10.1007/s11357-024-01159-3
pii: 10.1007/s11357-024-01159-3
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDCR NIH HHS
ID : DE032911
Pays : United States
Informations de copyright
© 2024. The Author(s), under exclusive licence to American Aging Association.
Références
Mariette X, Criswell LA. Primary Sjögren’s syndrome. N Engl J Med. 2018;378(10):931–9. https://doi.org/10.1056/NEJMc1804598 .
doi: 10.1056/NEJMc1804598
pubmed: 29514034
Retamozo S, Acar-Denizli N, Horváth IF, Ng WF, Rasmussen A, Dong X, Li X, Baldini C, Olsson P, Priori R, Seror R, Gottenberg JE, Kruize AA, Hernandez-Molina G, Vissink A, Sandhya P, Armagan B, Quartuccio L, Sebastian A, Praprotnik S, Bartoloni E, Kwok SK, Kvarnstrom M, Rischmueller M, Soláns-Laqué R, Sene D, Pasoto SG, Suzuki Y, Isenberg DA, Valim V, Nordmark G, Nakamura H, FernandesMoçaTrevisani V, Hofauer B, Sisó-Almirall A, Giacomelli R, Devauchelle-Pensec V, Bombardieri M, Atzeni F, Hammenfors D, Maure B, Carsons SE, Gheita T, Sánchez-Berná I, López-Dupla M, Morel J, Inanç N, Fonseca-Aizpuru E, Morcillo C, Vollenweider C, Melchor S, Vázquez M, Díaz-Cuiza E, Consani-Fernández S, de-Miguel-Campo B, Szántó A, Bombardieri S, Gattamelata A, Hinrichs A, Sánchez-Guerrero J, Danda D, Kilic L, De Vita S, Wiland P, Gerli R, Park SH, Wahren-Herlenius M, Bootsma H, Mariette X, Ramos-Casals M, Brito-Zerón P. Influence of the age at diagnosis in the disease expression of primary Sjögren syndrome. Analysis of 12,753 patients from the Sjögren Big Data Consortium. Clin Exp Rheumatol. 2021;39 Suppl 133(6):166–74. https://doi.org/10.55563/clinexprheumatol/egnd1i .
doi: 10.55563/clinexprheumatol/egnd1i
pubmed: 34919044
Turner MD. Hyposalivation and xerostomia: etiology, complications, and medical management. Dent Clin North Am. 2016;60(2):435–43. https://doi.org/10.1016/j.cden.2015.11.003 .
doi: 10.1016/j.cden.2015.11.003
pubmed: 27040294
Bjordal O, Norheim KB, Rødahl E, Jonsson R, Omdal R. Primary Sjögren’s syndrome and the eye. Surv Ophthalmol. 2020;65(2):119–32. https://doi.org/10.1016/j.survophthal.2019.10.004 .
doi: 10.1016/j.survophthal.2019.10.004
pubmed: 31634487
Goulabchand R, Castille E, Navucet S, Etchecopar-Etchart D, Matos A, Maria A, Gutierrez LA, Le Quellec A, de Champfleur NM, Gabelle A, Guilpain P. The interplay between cognition, depression, anxiety, and sleep in primary Sjogren’s syndrome patients. Sci Rep. 2022;12(1):13176. https://doi.org/10.1038/s41598-022-17354-1 .
doi: 10.1038/s41598-022-17354-1
pubmed: 35915312
pmcid: 9343365
Brito-Zerón P, Acar-Denizli N, Ng WF, Zeher M, Rasmussen A, Mandl T, Seror R, Li X, Baldini C, Gottenberg JE, Danda D, Quartuccio L, Priori R, Hernandez-Molina G, Armagan B, Kruize AA, Kwok SK, Kvarnström M, Praprotnik S, Sène D, Bartoloni E, Solans R, Rischmueller M, Suzuki Y, Isenberg DA, Valim V, Wiland P, Nordmark G, Fraile G, Bootsma H, Nakamura T, Giacomelli R, Devauchelle-Pensec V, Knopf A, Bombardieri M, Trevisani VF, Hammenfors D, Pasoto SG, Retamozo S, Gheita TA, Atzeni F, Morel J, Vollenveider C, Horvath IF, Sivils KL, Olsson P, De Vita S, Sánchez-Guerrero J, Kilic L, Wahren-Herlenius M, Mariette X, Ramos-Casals M. How immunological profile drives clinical phenotype of primary Sjögren’s syndrome at diagnosis: analysis of 10,500 patients (Sjögren Big Data Project). Clin Exp Rheumatol. 2018;36 Suppl 112(3):102–12.
pubmed: 30156539
Perera S, Ma L, Punwaney R, Ramachandran S. Clinical and cost burden of primary Sjögren’s syndrome: descriptive analysis using a US administrative claims database. J Health Econ Outcomes Res. 2018;5(2):150–61.
doi: 10.36469/9807
pubmed: 35620779
pmcid: 9090467
Thorlacius GE, Björk A, Wahren-Herlenius M. Genetics and epigenetics of primary Sjögren syndrome: implications for future therapies. Nat Rev Rheumatol. 2023;19(5):288–306. https://doi.org/10.1038/s41584-023-00932-6 .
doi: 10.1038/s41584-023-00932-6
pubmed: 36914790
pmcid: 10010657
Theander E, Jonsson R, Sjöström B, Brokstad K, Olsson P, Henriksson G. Prediction of Sjögren’s syndrome years before diagnosis and identification of patients with early onset and severe disease course by autoantibody profiling. Arthritis Rheumatol. 2015;67(9):2427–36. https://doi.org/10.1002/art.39214 .
doi: 10.1002/art.39214
pubmed: 26109563
Theander E, Vasaitis L, Baecklund E, Nordmark G, Warfvinge G, Liedholm R, Brokstad K, Jonsson R, Jonsson MV. Lymphoid organisation in labial salivary gland biopsies is a possible predictor for the development of malignant lymphoma in primary Sjögren’s syndrome. Ann Rheum Dis. 2011;70(8):1363–8. https://doi.org/10.1136/ard.2010.144782 .
doi: 10.1136/ard.2010.144782
pubmed: 21715359
Hao Y, O’Neill P, Naradikian MS, Scholz JL, Cancro MP. A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice. Blood. 2011;118:1294–304. https://doi.org/10.1182/blood-2011-01-330530 .
doi: 10.1182/blood-2011-01-330530
pubmed: 21562046
pmcid: 3152496
Rubtsov AV, Rubtsova K, Fischer A, Meehan RT, Gillis JZ, Kappler JW, Marrack P. Toll-like receptor 7 (TLR7)-driven accumulation of a novel CD11c
doi: 10.1182/blood-2011-01-331462
pubmed: 21543762
pmcid: 3152497
Rubtsova K, Rubtsov AV, Thurman JM, Mennona JM, Kappler JW, Marrack P. B cells expressing the transcription factor T-bet drive lupus-like autoimmunity. J Clin Invest. 2017;127(4):1392–404. https://doi.org/10.1172/JCI91250 .
doi: 10.1172/JCI91250
pubmed: 28240602
pmcid: 5373868
Saadoun D, Terrier B, Bannock J, Vazquez T, Massad C, Kang I, Joly F, Rosenzwajg M, Sene D, Benech P, Musset L, Klatzmann D, Meffre E, Cacoub P. Expansion of autoreactive unresponsive CD21-/low B cells in Sjögren’s syndrome-associated lymphoproliferation. Arthritis Rheum. 2013;65(4):1085–96. https://doi.org/10.1002/art.37828 .
doi: 10.1002/art.37828
pubmed: 23279883
pmcid: 4479193
Verstappen GM, Ice JA, Bootsma H, Pringle S, Haacke EA, de Lange K, van der Vries GB, Hickey P, Vissink A, Spijkervet FKL, Lessard CJ, Kroese FGM. Gene expression profiling of epithelium-associated FcRL4
doi: 10.1016/j.jaut.2020.102439
pubmed: 32201227
pmcid: 7337041
Punnanitinont A, Kasperek EM, Kiripolsky J, Zhu C, Miecznikowski JC, Kramer JM. TLR7 agonism accelerates disease in a mouse model of primary Sjögren’s syndrome and drives expansion of T-bet
doi: 10.3389/fimmu.2022.1034336
pubmed: 36591307
pmcid: 9799719
Hayashi Y, Utsuyama M, Kurashima C, Hirokawa K. Spontaneous development of organ-specific autoimmune lesions in aged C57BL/6 mice. Clin Exp Immunol. 1989;78(1):120–6.
pubmed: 2805415
pmcid: 1534591
Kurosawa M, Shikama Y, Furukawa M, Arakaki R, Ishimaru N, Matsushita K. Chemokines upregulated in epithelial cells control senescence-associated T cell accumulation in salivary glands of aged and Sjögren’s Syndrome model mice. Int J Mol Sci. 2021;22(5):2302. https://doi.org/10.3390/ijms22052302 .
doi: 10.3390/ijms22052302
pubmed: 33669065
pmcid: 7956724
Galletti JG, Scholand KK, Trujillo-Vargas CM, Yu Z, Mauduit O, Delcroix V, Makarenkova HP, de Paiva CS. Ectopic lymphoid structures in the aged lacrimal glands. Clin Immunol. 2023;248:109251. https://doi.org/10.1016/j.clim.2023.109251 .
doi: 10.1016/j.clim.2023.109251
pubmed: 36740002
pmcid: 10323865
Nusser A, Nuber N, Wirz OF, Rolink H, Andersson J, Rolink A. The development of autoimmune features in aging mice is closely associated with alterations of the peripheral CD4
doi: 10.1002/eji.201344408
pubmed: 25044476
Bagavant H, Trzeciak M, Papinska J, Biswas I, Dunkleberger ML, Sosnowska A, Deshmukh US. A method for the measurement of salivary gland function in mice. J Vis Exp. 2018;131:57203. https://doi.org/10.3791/57203 .
doi: 10.3791/57203
Papinska J, Bagavant H, Gmyrek GB, Sroka M, Tummala S, Fitzgerald KA, Deshmukh US. Activation of stimulator of interferon genes (STING) and Sjögren syndrome. J Dent Res. 2018;97(8):893–900. https://doi.org/10.1177/0022034518760855 .
doi: 10.1177/0022034518760855
pubmed: 29505322
pmcid: 6728552
Bagavant H, Trzeciak M, Biswas I, Papinska JA, Cizio K, Deshmukh US. Antibody deposition on vascular endothelial cells contributes to localized inflammation in salivary glands. J Oral Pathol Med. 2022;51(7):674–7. https://doi.org/10.1111/jop.13330 .
doi: 10.1111/jop.13330
pubmed: 35766433
pmcid: 9388553
Bagavant H, Deshmukh US. Protocols for experimental Sjögren’s Syndrome. Curr Protoc Immunol. 2020;131(1):e114. https://doi.org/10.1002/cpim.114 .
doi: 10.1002/cpim.114
pubmed: 33252847
pmcid: 8959043
Bankhead P, Loughrey MB, Fernández JA, Dombrowski Y, McArt DG, Dunne PD, McQuaid S, Gray RT, Murray LJ, Coleman HG, James JA, Salto-Tellez M, Hamilton PW. QuPath: open source software for digital pathology image analysis. Sci Rep. 2017;7(1):16878. https://doi.org/10.1038/s41598-017-17204-5 .
doi: 10.1038/s41598-017-17204-5
pubmed: 29203879
pmcid: 5715110
Bagavant H, Cizio K, Araszkiewicz AM, Papinska JA, Garman L, Li C, Pezant N, Drake WP, Montgomery CG, Deshmukh US. Systemic immune response to vimentin and granuloma formation in a model of pulmonary sarcoidosis. J Transl Autoimmun. 2022;5:100153. https://doi.org/10.1016/j.jtauto.2022.100153 .
doi: 10.1016/j.jtauto.2022.100153
pubmed: 35434591
pmcid: 9006845
Mekada K, Yoshiki A. Substrains matter in phenotyping of C57BL/6 mice. Exp Anim. 2021;70(2):145–60. https://doi.org/10.1538/expanim.20-0158 .
doi: 10.1538/expanim.20-0158
pubmed: 33441510
pmcid: 8150240
Bharaj TK, Aqrawi LA, Fromreide S, Jonsson R, Brun JG, Appel S, Skarstein K. Inflammatory stratification in primary Sjögren’s syndrome reveals novel immune cell alterations in patients’ minor salivary glands. Front Immunol. 2021;12:701581. https://doi.org/10.3389/fimmu.2021.701581 .
doi: 10.3389/fimmu.2021.701581
pubmed: 34322130
pmcid: 8311440
Phalke S, Rivera-Correa J, Jenkins D, Flores Castro D, Giannopoulou E, Pernis AB. Molecular mechanisms controlling age-associated B cells in autoimmunity. Immunol Rev. 2022;307(1):79–100. https://doi.org/10.1111/imr.13068 .
doi: 10.1111/imr.13068
pubmed: 35102602
Flurkey K, Currer JM, Harrison DE. Mouse models in aging research. The mouse in biomedical research. 2nd edition. 2007;3:637–72.
Groom JR, Luster AD. CXCR3 in T cell function. Exp Cell Res. 2011;317(5):620–31. https://doi.org/10.1016/j.yexcr.2010.12.017 .
doi: 10.1016/j.yexcr.2010.12.017
pubmed: 21376175
pmcid: 3065205
Ogawa N, Kawanami T, Shimoyama K, Ping L, Sugai S. Expression of interferon-inducible T cell alpha chemoattractant (CXCL11) in the salivary glands of patients with Sjögren’s syndrome. Clin Immunol. 2004;112(3):235–8. https://doi.org/10.1016/j.clim.2004.03.008 .
doi: 10.1016/j.clim.2004.03.008
pubmed: 15308116
Yoon KC, Park CS, You IC, Choi HJ, Lee KH, Im SK, Park HY, Pflugfelder SC. Expression of CXCL9, -10, -11, and CXCR3 in the tear film and ocular surface of patients with dry eye syndrome. Invest Ophthalmol Vis Sci. 2010;51(2):643–50. https://doi.org/10.1167/iovs.09-3425 .
doi: 10.1167/iovs.09-3425
pubmed: 19850844
pmcid: 3258976
Zhou J, Yu Q. Disruption of CXCR3 function impedes the development of Sjögren’s syndrome-like xerostomia in non-obese diabetic mice. Lab Invest. 2018;98(5):620–8. https://doi.org/10.1038/s41374-017-0013-4 .
doi: 10.1038/s41374-017-0013-4
pubmed: 29348563
pmcid: 7650019
Lin T, Walker GB, Kurji K, Fang E, Law G, Prasad SS, Kojic L, Cao S, White V, Cui JZ, Matsubara JA. Parainflammation associated with advanced glycation endproduct stimulation of RPE in vitro: implications for age-related degenerative diseases of the eye. Cytokine. 2013;62(3):369–81. https://doi.org/10.1016/j.cyto.2013.03.027 .
doi: 10.1016/j.cyto.2013.03.027
pubmed: 23601964
pmcid: 3947380
Bénézech C, Luu NT, Walker JA, Kruglov AA, Loo Y, Nakamura K, Zhang Y, Nayar S, Jones LH, Flores-Langarica A, McIntosh A, Marshall J, Barone F, Besra G, Miles K, Allen JE, Gray M, Kollias G, Cunningham AF, Withers DR, Toellner KM, Jones ND, Veldhoen M, Nedospasov SA, McKenzie ANJ, Caamaño JH. Inflammation-induced formation of fat-associated lymphoid clusters. Nat Immunol. 2015;16(8):819–28. https://doi.org/10.1038/ni.3215 .
doi: 10.1038/ni.3215
pubmed: 26147686
pmcid: 4512620
Kapsogeorgou EK, Abu-Helu RF, Moutsopoulos HM, Manoussakis MN. Salivary gland epithelial cell exosomes: A source of autoantigenic ribonucleoproteins. Arthritis Rheum. 2005;52(5):1517–21. https://doi.org/10.1002/art.21005 .
doi: 10.1002/art.21005
pubmed: 15880835
Kelly KM, Zhuang H, Nacionales DC, Scumpia PO, Lyons R, Akaogi J, Lee P, Williams B, Yamamoto M, Akira S, Satoh M, Reeves WH. “Endogenous adjuvant” activity of the RNA components of lupus autoantigens Sm/RNP and Ro 60. Arthritis Rheum. 2006;54(5):1557–67. https://doi.org/10.1002/art.21819 .
doi: 10.1002/art.21819
pubmed: 16645989
Baumgarth N. The double life of a B-1 cell: self-reactivity selects for protective effector functions. Nat Rev Immunol. 2011;11(1):34–46. https://doi.org/10.1038/nri2901 .
doi: 10.1038/nri2901
pubmed: 21151033
Yang Y, Tung JW, Ghosn EE, Herzenberg LA, Herzenberg LA. Division and differentiation of natural antibody-producing cells in mouse spleen. Proc Natl Acad Sci U S A. 2007;104(11):4542–6. https://doi.org/10.1073/pnas.0700001104 .
doi: 10.1073/pnas.0700001104
pubmed: 17360560
pmcid: 1838637
Mouat IC, Goldberg E, Horwitz MS. Age-associated B cells in autoimmune diseases. Cell Mol Life Sci. 2022;79(8):402. https://doi.org/10.1007/s00018-022-04433-9 .
doi: 10.1007/s00018-022-04433-9
pubmed: 35798993
pmcid: 9263041
Li ZY, Cai ML, Qin Y, Chen Z. Age/autoimmunity-associated B cells in inflammatory arthritis: an emerging therapeutic target. Front Immunol. 2023;14:1103307. https://doi.org/10.3389/fimmu.2023.1103307 .
doi: 10.3389/fimmu.2023.1103307
pubmed: 36817481
pmcid: 9933781
Haacke EA, Bootsma H, Spijkervet FKL, Visser A, Vissink A, Kluin PM, Kroese FGM. FcRL4
doi: 10.1016/j.jaut.2017.03.012
pubmed: 28390747
Punnanitinont A, Kasperek EM, Zhu C, Yu G, Miecznikowski JC, Kramer JM. TLR7 activation of age-associated B cells mediates disease in a mouse model of primary Sjögren’s disease. J Leukoc Biol. 2023;135. https://doi.org/10.1093/jleuko/qiad135 .
Kaklamanos A, Goules AV, Tzioufas AG. Experimental models of Sjögren’s syndrome: differences and similarities with human disease. Clin Exp Rheumatol. 2022;40(12):2398–412. https://doi.org/10.55563/clinexprheumatol/d4cx78 .
doi: 10.55563/clinexprheumatol/d4cx78
pubmed: 36305363
Allushi B, Bagavant H, Papinska J, Deshmukh US. Hyperglycemia and salivary gland dysfunction in the non-obese diabetic mouse: caveats for preclinical studies in Sjögren’s syndrome. Sci Rep. 2019;9(1):17969. https://doi.org/10.1038/s41598-019-54410-9 .
doi: 10.1038/s41598-019-54410-9
pubmed: 31784615
pmcid: 6884560