Circulating γδT-lymphocytes subsets in patients with inflammatory bowel diseases

  • Dmitry А. Tsekhanovich
  • Darya B. Nizheharodava
  • Andrey M. Starastsin
  • Aleg G. Dybau
  • Alexander V. Vorobei
  • Marina M. Zafranskaya

Abstract

Due to the high growth of inflammatory bowel diseases (Crohn’s disease and ulcerative colitis) with unfavorable environmental factors in the background, studies of immunopathogenetic mechanisms including T-cells response resulted in gastrointestinal tract damage are of immediate interest. γδT-lymphocytes are of particular importance as their role in the dysregulation of the innate and acquired immune response to commensal bacteria in genetically susceptible people has not yet been fully studied. This paper presents the quantitative and functional parameters of γδT-lymphocytes in patients with Crohn’s disease and ulcerative colitis, indicating an enhancement of immunological surveillance in inflammatory bowel diseases. The increase of the cytotoxic and activation phenotype expression in circulating γδT-lymphocytes as well as a redistribution of their composition with dominating of tissue-resident cells subsets were revealed in patients what may be key links in the immunopathogenesis of Crohn’s disease and ulcerative colitis. The established correlations with the severity of diseases allow to consider the use of phenotypic and functional γδT-lymphocytes features as diagnostic and prognostic markers for the development of autoimmune inflammation as well as for a differential diagnosis of gut autoimmune pathology. While γδT-lymphocytes themselves can be used as a therapeutic target in the development of new protocols for the pathogenetic therapy of inflammatory bowel diseases.

References

  1. Ma R, Yuan D, Guo Y, Yan R, & Li K. Immune effects of γδ T-Cells in colorectal cancer: A Review. Frontiers in Immunology. 2020;11:1600. DOI: 10.3389/fimmu.2020.01600.
  2. Do JS, Kim S, Keslar K, Jang E, Huang E, Fairchild RL, Pizarro TT, Min B. γδ T-Cells coexpressing gut homing α4β7 and αE integrins define a novel subset promoting intestinal inflammation. Journal of Immunology. 2017;198(2):908–915. DOI: 10.4049/jimmunol.1601060.
  3. McCarthy NE and Eberl M. Human γδ T-Cell сontrol of mucosal immunity and inflammation. Frontiers in Immunology. 2018;9:985. DOI: 10.3389/fimmu.2018.00985.
  4. Ribot JC, Lopes N, & Silva-Santos B. γδ T cells in tissue physiology and surveillance. Nature Reviews Immunology. 2021;21:221–232. DOI:10.1038/s41577-020-00452-4.
  5. Fay NS, Larson EC and Jameson JM. Chronic Inflammation and γδ T Cells. Frontiers in Immunology. 2016;7:210. DOI: 10.3389/fimmu.2016.00210.
  6. Akitsu A, & Iwakura Y. Interleukin-17-producing γδ T (γδ17) cells in inflammatory diseases. Journal of Immunology. 2018;155(4):418–426. DOI: 10.1111/imm.12993.
  7. Kühl AA, Pawlowski NN, Grollich K, Loddenkemper C, Zeitz M, Hoffmann JC. Aggravation of intestinal inflammation by depletion/deficiency of gammadelta T cells in different types of IBD animal models. Journal of Leukocyte Biology. 2007;81(1):168–75. DOI: 10.1189/jlb.1105696.
  8. Cheroute H, Lambolez F, Mucida D. The light and dark sides of intestinal intraepithelial lymphocytes. Nature Reviews Immunology. 2011;11(7):445–456. DOI:10.1038/nri3007.
  9. Lu Y, Li X, Liu S, Zhang Y, Zhang D. Toll-like Receptors and Inflammatory Bowel Disease. Frontiers in Immunology. 2018;30;9:72. DOI: 10.3389/fimmu.2018.00072.
  10. La Scaleia R, Stoppacciaro A, Oliva S, Morrone S, Di Nardo G, Santoni A, Cucchiara S, Palmieri G. NKG2D/Ligand dysregulation and functional alteration of innate immunity cell populations in pediatric IBD. Inflammmatory Bowel Diseases. 2012;18(10):1910–22. DOI: 10.1002/ibd.22899.
  11. Vantourout P, Hayday A. Six-of-the-best: unique contributions of γδ T cells to immunology. Nature Reviews Immunology. 2013;13(2):88–100. DOI: 10.1038/nri3384.
  12. Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein CN, Brant SR, et al. Toward an Integrated Clinical, Molecular and Serological Classification of Inflammatory Bowel Disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Canadian Journal of Gastroenterology. 2005;19(supplА):5A–36A. DOI:10.1155/2005/269076.
  13. Guan Q. A Comprehensive review and update on the pathogenesis of inflammatory bowel disease. Journal of Immunology Research. 2019; article ID7247238. DOI: 10.1155/2019/7247238.
  14. Catalan-Serra I, Sandvik A, Bruland T. Gammadelta T-Cells in Crohn’s Disease: a new player in the disease pathogenesis? Journal of Crohn’s and Colitis. 2017;11(9):1135–1145. DOI: 10.1093/ecco-jcc/jjx039.
  15. Presti E, Mitri M, Mocciaro F. Characterization of γδ T-Cells in intestinal mucosa from patients with early-onset or long-standing inflammatory bowel disease and their correlation with clinical status. Journal of Crohn’s and Colitis. 2019;13(7):873–883. DOI: 10.1093/ecco-jcc/jjz015.
  16. Gryglewski А, Richter P, Szczepanik M. Changes in γδ T-Cells in peripheral blood of patients with Ulcerative Colitis exacerbations. Archivum Immunologiae et Therapiae Experimentalis. 2021;69(1):18. DOI: 10.1007/s00005-021-00620-x.
  17. Wu D, Wu P, Qiu F, Wei Q, Huang J. Human γδT-cell subsets and their involvement in tumor immunity. Cellular & Molecular Immunology. 2017;14(3):245–253. DOI: 10.1038/cmi.2016.55.
  18. Mann E, McCarthy E, Peake S. Skin- and gut-homing molecules on human circulating γδ T-cells and their dysregulation in inflammatory bowel disease. Clinical & Experimental Immunology. 2012;170(2):122–30. DOI: 10.1111/j.1365-2249.2012.04649.x.
  19. Kulkarni N, Pathak M, Lal G. Role of chemokine receptors and intestinal epithelial cells in the mucosal inflammation and tolerance. Journal of Leukocyte Biology. 2017;101(2):377–394. DOI: 10.1189/jlb.1RU0716-327R.
  20. Jhita N, Raikar SS. Allogeneic gamma delta T cells as adoptive cellular therapy for hematologic malignancies. Journal of Immunology. 2022;2(3):334–350. DOI: 10.37349/ei.2022.00054.
  21. Li M, Guo W, Dong Y, Wang X, Dai D, Liu X, et al.. Elevated Exhaustion Levels of NK and CD8+ T Cells as Indicators for Progression and Prognosis of COVID-19 Disease. Frontiers in Immunology. 2020;14(11):580237. DOI: 10.3389/fimmu.2020.580237.
  22. Fernandes P, MacSharry J, Darby T, Fanning A, Shanahan F, Houston A, & Brint E. Differential expression of key regulators of Toll-like receptors in ulcerative colitis and Crohn’s disease: a role for Tollip and peroxisome proliferator-activated receptor gamma? Clinical & Experimental Immunology. 2015;183(3):358–368. DOI:10.1111/cei.12732.
  23. Stojanovic A, Correia MP and Cerwenka A. The NKG2D/ NKG2DL Axis in the Crosstalk Between Lymphoid and Myeloid Cells in Health and Disease. Frontiers in Immunology. 2018;9:827. DOI: 10.3389/fimmu.2018.00827.
  24. Pariente B, Mocan I, Camus M, Dutertre CA, Ettersperger J, Cattan P, et al. Activation of the receptor NKG2D leads to production of Th17 cytokines in CD4+ T cells of patients with Crohn’s disease. Gastroenterology. 2011;141(1):217–226.e1-2. DOI: 10.1053/j.gastro.2011.03.061.
  25. Cohavy O, & Targan SR. CD56 Marks an Effector T Cell Subset in the Human Intestine. Journal of Immunology. 2007;178(9), 5524–5532. DOI:10.4049/jimmunol.178.9.5524.
  26. Ng S, Plamondon S, Al-Hassi O. A novel population of human CD56+ human leucocyte antigen D-related (HLA-DR+) colonic lamina propria cells is associated with inflammation in ulcerative colitis. Clinical & Experimental Immunology. 2009;158(2):205–218. DOI: 10.1111/j.1365–2249.2009.04012.x.
  27. Gully B, Rossjohn J, Davey M. Our evolving understanding of the role of the γδ T cell receptor in γδ T cell mediated immunity. Biochemical Society. 2021;49(5):1985–1995. DOI: 10.1042/BST20200890.
Published
2023-11-08
Keywords: inflammatory bowel disease, autoimmune pathology, environmental factor, γδT-lymphocytes, flow cytometry
How to Cite
Tsekhanovich, D., Nizheharodava, D., Starastsin, A., Dybau, A., Vorobei, A., & Zafranskaya, M. (2023). Circulating γδT-lymphocytes subsets in patients with inflammatory bowel diseases. Journal of the Belarusian State University. Ecology, 4. Retrieved from https://journals.bsu.by/index.php/ecology/article/view/5917