Investigation of the Relationship of Tissue-resident γδ T Cells and IL-17 Gene Expression with the Pathogenesis of Autoimmune Hepatitis

Overview

Journal Immunol Res

Specialty Allergy & Immunology

Date 2024 Jul 18

PMID 39023823

Authors

Nurullah Yucel

Gulam Hekimoglu

Sevinc Keser

Selma Erhan

Gamze Yesilay

Gulizar Hocaoglu

Muzaffer Seker

Affiliations

Soon will be listed here.

Abstract

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease. Elevated serum immunoglobulin G (IgG) levels, autoantibodies, and histopathological interface hepatitis are the hallmarks of AIH. Autoantibodies and pathological findings, clinical and biochemical features, typical immunoglobulin levels, and exclusion of other diseases are used to diagnose the condition. Gamma-delta (γδ) T cells are a unique population of unconventional T cells with γ and δ glycoprotein chains. γδ T cells have been shown to play a crucial role in autoimmune diseases by producing interleukin (IL)-17. However, its role in AIH remains to be further elucidated. In this study, we aimed to examine the role of γδ T cells and IL-17 in the pathogenesis of AIH, by working on biopsy samples. Paraffin blocks of 18 patients with type 1 AIH and 18 control liver tissues were analyzed. qRT-PCR assessed IL-17 gene expression. Immunofluorescence double staining of CD3TCRγδ was performed to reveal tissue-resident γδ T cells' role in AIH. When comparing AIH to the control, there was a substantial increase in the ratio of CD3TCRγδ cells in total inflammatory cells (p = 0.01). IL-17 gene expression was lowered in AIH when compared to the control (p = 0.01). This study provides evidence for the involvement of γδ T cells and IL-17 in the pathogenesis of AIH. The ratio of γδ T cells and IL-17 gene expression showed a significant difference in AIH suggesting a potential role for γδ T cells in driving liver inflammation in A fIH.

References

Vergani D, Mieli-Vergani G . The impact of autoimmunity on hepatocytes. Semin Liver Dis. 2007; 27(2):140-51. DOI: 10.1055/s-2007-979467. View

Giri S, Lal G . Differentiation and functional plasticity of gamma-delta (γδ) T cells under homeostatic and disease conditions. Mol Immunol. 2021; 136:138-149. DOI: 10.1016/j.molimm.2021.06.006. View

Nielsen M, Witherden D, Havran W . γδ T cells in homeostasis and host defence of epithelial barrier tissues. Nat Rev Immunol. 2017; 17(12):733-745. PMC: 5771804. DOI: 10.1038/nri.2017.101. View

Paul S, Lal G . Regulatory and effector functions of gamma-delta (γδ) T cells and their therapeutic potential in adoptive cellular therapy for cancer. Int J Cancer. 2016; 139(5):976-85. DOI: 10.1002/ijc.30109. View

Paul S, Singh A, Shilpi , Lal G . Phenotypic and functional plasticity of gamma-delta (γδ) T cells in inflammation and tolerance. Int Rev Immunol. 2013; 33(6):537-58. DOI: 10.3109/08830185.2013.863306. View

Mills K . IL-17 and IL-17-producing cells in protection versus pathology. Nat Rev Immunol. 2022; 23(1):38-54. PMC: 9255545. DOI: 10.1038/s41577-022-00746-9. View

Cardona A, Teale J . Gamma/delta T cell-deficient mice exhibit reduced disease severity and decreased inflammatory response in the brain in murine neurocysticercosis. J Immunol. 2002; 169(6):3163-71. DOI: 10.4049/jimmunol.169.6.3163. View

Xi C, Jia Z, Xiaoli W, Na Z, He W, Hao J . New Aspect of Liver IL-17γδ T Cells. Mol Immunol. 2019; 107:41-43. DOI: 10.1016/j.molimm.2018.12.030. View

Rampoldi F, Brunk F, Bonrouhi M, Federico G, Krunic D, Porubsky S . Deficiency of N-myristoylation reveals calcineurin activity as regulator of IFN-γ-producing γδ T cells. J Leukoc Biol. 2017; 101(4):1005-1014. DOI: 10.1189/jlb.1A0616-264R. View

10.

Campe J, Ullrich E . T Helper Cell Lineage-Defining Transcription Factors: Potent Targets for Specific GVHD Therapy?. Front Immunol. 2022; 12:806529. PMC: 8766661. DOI: 10.3389/fimmu.2021.806529. View

11.

Brandes M, Willimann K, Moser B . Professional antigen-presentation function by human gammadelta T Cells. Science. 2005; 309(5732):264-8. DOI: 10.1126/science.1110267. View

12.

Rubino S, Mayo L, Wimmer I, Siedler V, Brunner F, Hametner S . Acute microglia ablation induces neurodegeneration in the somatosensory system. Nat Commun. 2018; 9(1):4578. PMC: 6212411. DOI: 10.1038/s41467-018-05929-4. View

13.

Martins E, Graham A, Chapman R, Fleming K . Elevation of gamma delta T lymphocytes in peripheral blood and livers of patients with primary sclerosing cholangitis and other autoimmune liver diseases. Hepatology. 1996; 23(5):988-93. DOI: 10.1002/hep.510230508. View

14.

Liu F, Zheng H, Qi Y, Wang X, Yang J, Han M . PFA-fixed Hsp60sp-loaded dendritic cells as a vaccine for the control of mouse experimental allergic encephalomyelitis. Cell Mol Immunol. 2013; 11(2):169-74. PMC: 4003379. DOI: 10.1038/cmi.2013.58. View

15.

Muratori L, Muratori P, Lanzoni G, Ferri S, Lenzi M . Application of the 2010 American Association for the study of liver diseases criteria of remission to a cohort of Italian patients with autoimmune hepatitis. Hepatology. 2010; 52(5):1857. DOI: 10.1002/hep.23924. View

16.

Chen B, Wu Y, Tanaka Y, Zhang W . Small molecules targeting c-Myc oncogene: promising anti-cancer therapeutics. Int J Biol Sci. 2014; 10(10):1084-96. PMC: 4202025. DOI: 10.7150/ijbs.10190. View

17.

Chen D, Cao Y, Li H, Kim D, Ahsan N, Thelen J . Extracellular ATP elicits DORN1-mediated RBOHD phosphorylation to regulate stomatal aperture. Nat Commun. 2017; 8(1):2265. PMC: 5741621. DOI: 10.1038/s41467-017-02340-3. View

18.

Meng F, Wang K, Aoyama T, Grivennikov S, Paik Y, Scholten D . Interleukin-17 signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice. Gastroenterology. 2012; 143(3):765-776.e3. PMC: 3635475. DOI: 10.1053/j.gastro.2012.05.049. View

19.

Bonneville M, OBrien R, Born W . Gammadelta T cell effector functions: a blend of innate programming and acquired plasticity. Nat Rev Immunol. 2010; 10(7):467-78. DOI: 10.1038/nri2781. View

20.

Ribot J, Lopes N, Silva-Santos B . γδ T cells in tissue physiology and surveillance. Nat Rev Immunol. 2020; 21(4):221-232. DOI: 10.1038/s41577-020-00452-4. View