#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Immunopathogenesis of canine chronic ulcerative stomatitis


Autoři: J. G. Anderson aff001;  A. Kol aff002;  P. Bizikova aff003;  B. P. Stapelton aff004;  K. Ford aff004;  A. Villarreal aff002;  R. J. Jimenez aff002;  D Vasilatis aff002;  B. G. Murphy aff002
Působiště autorů: Sacramento Veterinary Dental Services, Rancho Cordova, California, United States of America aff001;  Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America aff002;  Department of Clinical Sciences, College of Veterinary Medicine, NC State University, Raleigh, North Carolina, United States of America aff003;  Barrington Animal Hospital, Barrington, Illinois, United States of America aff004
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0227386

Souhrn

Canine Chronic Ulcerative Stomatitis is a spontaneously occurring inflammatory disease of the oral mucosa. An immune-mediated pathogenesis is suspected though not yet proven. We have recently reported on the clinical and histologic features, and identification of select leukocyte cell populations within the lesion. A clinical and histologic similarity to oral lichen planus of people was proposed. In the present study, these initial observations are extended by examining lesions from 24 dogs with clinical evidence of chronic ulcerative stomatitis. Because dogs with chronic ulcerative stomatitis often have concurrent periodontal disease, we wondered if dental plaque/biofilm may be a common instigator of inflammation in both lesions. We hypothesized that dogs with chronic ulcerative stomatitis would exhibit a spectrum of pathologic changes and phenotype of infiltrating leukocytes that would inform lesion pathogenesis and that these changes would differ from inflammatory phenotypes in periodontitis. Previously we identified chronic ulcerative stomatitis lesions to be rich in FoxP3+ and IL17+ cells. As such, we suspect that these leukocytes play an important role in lesion pathogenesis. The current study confirms the presence of moderate to large numbers of FoxP3+ T cells and IL17+ cells in all ulcerative stomatitis lesions using confocal immunofluorescence. Interestingly, the majority of IL17+ cells were determined to be non-T cells and IL17+ cell frequencies were negatively correlated with severity on the clinical scoring system. Three histologic subtypes of ulcerative stomatitis were determined; lichenoid, deep stomatitis and granulomatous. Periodontitis lesions, like stomatitis lesions, were B cell and plasma cell rich, but otherwise differed from the stomatitis lesions. Direct immunofluorescence results did not support an autoantibody-mediated autoimmune disease process. This investigation contributes to the body of literature regarding leukocyte involvement in canine idiopathic inflammatory disease pathogenesis.

Klíčová slova:

Dogs – White blood cells – T cells – Lesions – Inflammatory diseases – Immunohistochemistry techniques – Pathogenesis – Histology


Zdroje

1. Anderson JG, Peralta S, Kol A, Kass PH, Murphy B. Clinical and Histopathologic Characterization of Canine Chronic Ulcerative Stomatitis. Vet Pathol. 2017;54(3):511–9. Epub 2017/01/24. doi: 10.1177/0300985816688754 28113036.

2. Tesmer LA, Lundy SK, Sarkar S, Fox DA. Th17 cells in human disease. Immunol Rev. 2008;223:87–113. Epub 2008/07/11. doi: 10.1111/j.1600-065X.2008.00628.x 18613831; PubMed Central PMCID: PMC3299089.

3. Gaffen SL, Hajishengallis G. A new inflammatory cytokine on the block: re-thinking periodontal disease and the Th1/Th2 paradigm in the context of Th17 cells and IL-17. J Dent Res. 2008;87(9):817–28. Epub 2008/08/23. doi: 10.1177/154405910808700908 18719207; PubMed Central PMCID: PMC2692983.

4. Mailer RKW. Alternative Splicing of FOXP3-Virtue and Vice. Front Immunol. 2018;9:530. Epub 2018/03/30. doi: 10.3389/fimmu.2018.00530 29593749; PubMed Central PMCID: PMC5859138.

5. Chellappa S, Hugenschmidt H, Hagness M, Line PD, Labori KJ, Wiedswang G, et al. Regulatory T cells that co-express RORgammat and FOXP3 are pro-inflammatory and immunosuppressive and expand in human pancreatic cancer. Oncoimmunology. 2016;5(4):e1102828. Epub 2016/05/04. doi: 10.1080/2162402X.2015.1102828 27141387; PubMed Central PMCID: PMC4839385.

6. Zhou L, Cao T, Wang Y, Yao H, Du G, Chen G, et al. Frequently Increased but Functionally Impaired CD4+CD25+ Regulatory T Cells in Patients with Oral Lichen Planus. Inflammation. 2016;39(3):1205–15. Epub 2016/04/24. doi: 10.1007/s10753-016-0356-9 27106476.

7. Junginger J, Schwittlick U, Lemensieck F, Nolte I, Hewicker-Trautwein M. Immunohistochemical investigation of Foxp3 expression in the intestine in healthy and diseased dogs. Vet Res. 2012;43:23. doi: 10.1186/1297-9716-43-23 22440243; PubMed Central PMCID: PMC3364872.

8. Maeda S, Ohno K, Fujiwara-Igarashi A, Uchida K, Tsujimoto H. Changes in Foxp3-Positive Regulatory T Cell Number in the Intestine of Dogs With Idiopathic Inflammatory Bowel Disease and Intestinal Lymphoma. Vet Pathol. 2016;53(1):102–12. doi: 10.1177/0300985815591081 26173451.

9. Harvey CE. Management of periodontal disease: understanding the options. Vet Clin North Am Small Anim Pract. 2005;35(4):819–36, vi. Epub 2005/06/28. doi: 10.1016/j.cvsm.2005.03.002 15979515.

10. Graves DT, Cochran D. The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction. J Periodontol. 2003;74(3):391–401. Epub 2003/04/25. doi: 10.1902/jop.2003.74.3.391 12710761.

11. Garlet GP, Cardoso CR, Silva TA, Ferreira BR, Avila-Campos MJ, Cunha FQ, et al. Cytokine pattern determines the progression of experimental periodontal disease induced by Actinobacillus actinomycetemcomitans through the modulation of MMPs, RANKL, and their physiological inhibitors. Oral Microbiol Immunol. 2006;21(1):12–20. Epub 2006/01/05. doi: 10.1111/j.1399-302X.2005.00245.x 16390336.

12. Bellows J, Berg ML, Dennis S, Harvey R, Lobprise HB, Snyder CJ, et al. 2019 AAHA Dental Care Guidlines for Dogs and Cats https://www.aaha.org/guidelines/dental_guidelines/default.aspx2019 [June 20th, 2019].

13. Keller SM, Vernau W, Hodges J, Kass PH, Vilches-Moure JG, McElliot V, et al. Hepatosplenic and Hepatocytotropic T-Cell Lymphoma: Two Distinct Types of T-Cell Lymphoma in Dogs. Vet Pathol. 2013;50(2):281–90. doi: 10.1177/0300985812451625 WOS:000330296500012. 22711745

14. Sueiro FA, Alessi AC, Vassallo J. Canine lymphomas: a morphological and immunohistochemical study of 55 cases, with observations on p53 immunoexpression. J Comp Pathol. 2004;131(2–3):207–13. Epub 2004/07/28. doi: 10.1016/j.jcpa.2004.04.002 15276860.

15. Noland EL, Keller SM, Kiupel M. Subcutaneous Panniculitis-Like T-cell Lymphoma in Dogs: Morphologic and Immunohistochemical Classification. Vet Pathol. 2018;55(6):802–8. Epub 2018/08/04. doi: 10.1177/0300985818789474 30071780.

16. Moore PF, Rossitto PV, Danilenko DM, Wielenga JJ, Raff RF, Severns E. Monoclonal-Antibodies Specific for Canine Cd4 and Cd8 Define Functional Lymphocyte-T Subsets and High-Density Expression of Cd4 by Canine Neutrophils. Tissue Antigens. 1992;40(2):75–85. doi: 10.1111/j.1399-0039.1992.tb01963.x WOS:A1992JH20700004. 1412420

17. Biller BJ, Elmslie RE, Burnett RC, Avery AC, Dow SW. Use of FoxP3 expression to identify regulatory T cells in healthy dogs and dogs with cancer. Vet Immunol Immunop. 2007;116(1–2):69–78. doi: 10.1016/j.vetimm.2006.12.002 WOS:000245259300007. 17224188

18. Pinheiro D, Singh Y, Grant CR, Appleton RC, Sacchini F, Walker KRL, et al. Phenotypic and functional characterization of a CD4(+) CD25(high) FOXP3(high) regulatory T-cell population in the dog. Immunology. 2011;132(1):111–22. doi: 10.1111/j.1365-2567.2010.03346.x WOS:000285064200013. 20880379

19. Kol A, Walker NJ, Nordstrom M, Borjesson DL. Th17 Pathway As a Target for Multipotent Stromal Cell Therapy in Dogs: Implications for Translational Research. PLoS One. 2016;11(2):e0148568. doi: 10.1371/journal.pone.0148568 26872054.

20. Jubala CM, Wojcieszyn JW, Valli VEO, Getzy DM, Fosmire SP, Coffey D, et al. CD20 expression in normal canine B cells and in canine non-Hodgkin lymphoma. Vet Pathol. 2005;42(4):468–76. doi: 10.1354/vp.42-4-468 WOS:000230282600008. 16006606

21. Ramos-Vara JA, Miller MA, Valli VE. Immunohistochemical detection of multiple myeloma 1/interferon regulatory factor 4 (MUM1/IRF-4) in canine plasmacytoma: comparison with CD79a and CD20. Vet Pathol. 2007;44(6):875–84. Epub 2007/11/28. doi: 10.1354/vp.44-6-875 18039900.

22. Stilwell JM, Rissi DR. Immunohistochemical Labeling of Multiple Myeloma Oncogene I/Interferon Regulatory Factor 4 (MUMI/IRF-4) in Canine Cutaneous Histiocytoma. Vet Pathol. 2018;55(4):517–20. doi: 10.1177/0300985818759770 WOS:000436075800007. 29444632

23. Kato Y, Murakami M, Hoshino Y, Mori T, Maruo K, Hirata A, et al. The class A macrophage scavenger receptor CD204 is a useful immunohistochemical marker of canine histiocytic sarcoma. J Comp Pathol. 2013;148(2–3):188–96. Epub 2012/08/21. doi: 10.1016/j.jcpa.2012.06.009 22901707.

24. Wagner A, Junginger J, Lemensieck F, Hewicker-Trautwein M. Immunohistochemical characterization of gastrointestinal macrophages/phagocytes in dogs with inflammatory bowel disease (IBD) and non-IBD dogs. Vet Immunol Immunopathol. 2018;197:49–57. Epub 2018/02/25. doi: 10.1016/j.vetimm.2018.01.011 29475506.

25. Gibson-Corley KN, Olivier AK, Meyerholz DK. Principles for valid histopathologic scoring in research. Vet Pathol. 2013;50(6):1007–15. doi: 10.1177/0300985813485099 23558974; PubMed Central PMCID: PMC3795863.

26. Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 Cells. Annu Rev Immunol. 2009;27:485–517. Epub 2009/01/10. doi: 10.1146/annurev.immunol.021908.132710 19132915.

27. Akitsu A, Iwakura Y. Interleukin-17-producing gammadelta T (gammadelta17) cells in inflammatory diseases. Immunology. 2018;155(4):418–26. Epub 2018/08/23. doi: 10.1111/imm.12993 30133701; PubMed Central PMCID: PMC6231014.

28. Papotto PH, Reinhardt A, Prinz I, Silva-Santos B. Innately versatile: gammadelta17 T cells in inflammatory and autoimmune diseases. J Autoimmun. 2018;87:26–37. Epub 2017/12/06. doi: 10.1016/j.jaut.2017.11.006 29203226.

29. Ramirez-Velazquez C, Castillo EC, Guido-Bayardo L, Ortiz-Navarrete V. IL-17-producing peripheral blood CD177+ neutrophils increase in allergic asthmatic subjects. Allergy Asthma Clin Immunol. 2013;9(1):23. Epub 2013/07/05. doi: 10.1186/1710-1492-9-23 23822853; PubMed Central PMCID: PMC3704811.

30. Crotty S. Follicular helper CD4 T cells (TFH). Annu Rev Immunol. 2011;29:621–63. Epub 2011/02/15. doi: 10.1146/annurev-immunol-031210-101400 21314428.

31. Zenobia C, Hajishengallis G. Basic biology and role of interleukin-17 in immunity and inflammation. Periodontol 2000. 2015;69(1):142–59. Epub 2015/08/08. doi: 10.1111/prd.12083 26252407; PubMed Central PMCID: PMC4530463.

32. Conti HR, Shen F, Nayyar N, Stocum E, Sun JN, Lindemann MJ, et al. Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. The Journal of Experimental Medicine. 2009;206(2):299–311. doi: 10.1084/jem.20081463 19204111

33. Lionakis MS, Netea MG, Holland SM. Mendelian Genetics of Human Susceptibility to Fungal Infection. Cold Spring Harbor Perspectives in Medicine. 2014;4(6). doi: 10.1101/cshperspect.a019638 24890837

34. Abusleme L, Moutsopoulos N. IL-17: overview and role in oral immunity and microbiome. Oral Diseases. 2017;23(7):854–65. doi: 10.1111/odi.12598 27763707

35. Hajishengallis G. Periodontitis: from microbial immune subversion to systemic inflammation. Nat Rev Immunol. 2015;15(1):30–44. Epub 2014/12/24. doi: 10.1038/nri3785 25534621; PubMed Central PMCID: PMC4276050.

36. Moutsopoulos NM, Zerbe CS, Wild T, Dutzan N, Brenchley L, DiPasquale G, et al. Interleukin-12 and Interleukin-23 Blockade in Leukocyte Adhesion Deficiency Type 1. New England Journal of Medicine. 2017;376(12):1141–6. doi: 10.1056/NEJMoa1612197 28328326.

37. Dutzan N, Konkel JE, Greenwell-Wild T, Moutsopoulos NM. Characterization of the human immune cell network at the gingival barrier. Mucosal immunology. 2016;9(5):1163–72. Epub 2016/01/07. doi: 10.1038/mi.2015.136 26732676; PubMed Central PMCID: PMC4820049.

38. Moutsopoulos NM, Kling HM, Angelov N, Jin W, Palmer RJ, Nares S, et al. Porphyromonas gingivalis promotes Th17 inducing pathways in chronic periodontitis. J Autoimmun. 2012;39(4):294–303. Epub 2012/05/09. doi: 10.1016/j.jaut.2012.03.003 22560973; PubMed Central PMCID: PMC3416947.

39. Hajishengallis G, Chavakis T. Endogenous modulators of inflammatory cell recruitment. Trends Immunol. 2013;34(1):1–6. Epub 2012/09/07. doi: 10.1016/j.it.2012.08.003 22951309; PubMed Central PMCID: PMC3703146.

40. Eke PI, Dye BA, Wei L, Thornton-Evans GO, Genco RJ, Cdc Periodontal Disease Surveillance workgroup: James Beck GDRP. Prevalence of periodontitis in adults in the United States: 2009 and 2010. J Dent Res. 2012;91(10):914–20. Epub 2012/09/01. doi: 10.1177/0022034512457373 22935673.

41. Eke PI, Wei L, Borgnakke WS, Thornton-Evans G, Zhang X, Lu H, et al. Periodontitis prevalence in adults ≥ 65 years of age, in the USA. Periodontology 2000. 2016;72(1):76–95. doi: 10.1111/prd.12145 27501492

42. Ohlrich EJ, Cullinan MP, Seymour GJ. The immunopathogenesis of periodontal disease. Aust Dent J. 2009;54 Suppl 1:S2–10. Epub 2009/09/10. doi: 10.1111/j.1834-7819.2009.01139.x 19737265.

43. Abe T, AlSarhan M, Benakanakere MR, Maekawa T, Kinane DF, Cancro MP, et al. The B Cell-Stimulatory Cytokines BLyS and APRIL Are Elevated in Human Periodontitis and Are Required for B Cell-Dependent Bone Loss in Experimental Murine Periodontitis. J Immunol. 2015;195(4):1427–35. Epub 2015/07/08. doi: 10.4049/jimmunol.1500496 26150532; PubMed Central PMCID: PMC4530049.

44. Javvadi LR, Parachuru VP, Milne TJ, Seymour GJ, Rich AM. Regulatory T-cells and IL17A(+) cells infiltrate oral lichen planus lesions. Pathology. 2016;48(6):564–73. Epub 2016/09/07. doi: 10.1016/j.pathol.2016.06.002 27594511.

45. Firth FA, Friedlander LT, Parachuru VP, Kardos TB, Seymour GJ, Rich AM. Regulation of immune cells in oral lichen planus. Arch Dermatol Res. 2015;307(4):333–9. doi: 10.1007/s00403-015-1540-8 25638329.

46. Lei L, Zhan L, Tan W, Chen S, Li Y, Reynolds M. Foxp3 gene expression in oral lichen planus: a clinicopathological study. Mol Med Rep. 2014;9(3):928–34. doi: 10.3892/mmr.2014.1919 24469541.

47. Buajeeb W, Okuma N, Thanakun S, Laothumthut T. Direct Immunofluorescence in Oral Lichen Planus. J Clin Diagn Res. 2015;9(8):ZC34–7. Epub 2015/10/06. doi: 10.7860/JCDR/2015/13510.6312 26436043; PubMed Central PMCID: PMC4576637.


Článok vyšiel v časopise

PLOS One


2020 Číslo 1
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#