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Relationship between TIM3 Expression on Peripheral T Lymphocytes and Post-Stroke Depression

Document Type : Original Article

Authors

1 Department of Clinical Laboratory, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, 310012, China.

2 Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, 311200, China.

3 Lishui TCM Hospital Affiliated to Zhejiang Chinese Medical University (Lishui Hospital of Traditional Chinese Medicine), Lishui, Zhejiang, 323000, China.

4 The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310006, China.

Abstract

Background: T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) is a regulatory molecule expressed on a variety of cell types, including CD3+ T cells. Few studies have been conducted to look into the correlation between TIM3 expression on peripheral T lymphocytes and post-stroke depression (PSD).
Objective: To investigate the relationship between TIM3 expressions on peripheral T lymphocytes in PSD patients.
Methods: Acute stroke patients without depression (NPSD) (n=65), PSD patients (n=23), and body mass index (BMI), age, and education-matched healthy controls (HC) (n=59) were enrolled. Using flow cytometry, TIM3 expression was examined in the peripheral CD3+ CD4+ and CD3+ CD8+ T lymphocytes. Evaluation of the depressive severity in PSD patients was assessed using a 17-item Hamilton Depression Rating Scale (HAM-D-17). We used enzyme-linked immunosorbent assay (ELISA) to determine the serum concentrations of IL-1β, IL-6, IL-10, and IL-18. We further assessed the relationships between TIM3 expression, serum cytokine levels, and the HAM-D-17 scores.
Results: CD3+ CD4+ T cells reduced significantly in PSD patients compared with the NPSD patients and HC. Both NPSD patients and PSD patients had a significant increase in TIM3 expression in their peripheral CD3+ CD4+ T lymphocytes, compared with HC. In PSD patients, a higher frequency of peripheral CD3+ CD8+ T lymphocytes showed significant expression of TIM3 compared to NPSD patients and HC. High TIM3 level on peripheral CD3+ CD8+ T lymphocytes was positively associated with the HAM-D score.
Conclusion: Patients with PSD exhibit immune dysfunction. TIM3 might contribute to the development and severity of PSD, making it a potential therapeutic target.

Keywords

References
  1. Guo J, Wang J, Sun W, Liu X. The advances of post-stroke depression: 2021 update. J Neurol. 2022; 269(3):1236-1249.
  2. Medeiros GC, Roy D, Kontos N, Beach SR. Post-stroke depression: A 2020 updated review. Gen Hosp Psychiatry. 2020; 66:70-80.
  3. Nagy EE, Frigy A, Szász JA, Horváth E. Neuroinflammation and microglia/macrophage phenotype modulate the molecular background of post-stroke depression: A literature review. Exp Ther Med. 2020; 20(3):2510-2523.
  4. Zhou L, Wang T, Yu Y, Li M, Sun X, Song W, et al. The etiology of poststroke-depression: a hypothesis involving HPA axis. Biomed Pharmacother. 2022; 151:113146.
  5. Croese T, Castellani G, Schwartz M. Immune cell compartmentalization for brain surveillance and protection. Nat Immunol. 2021; 22(9):1083-1092.
  6. Ribot JC, Lopes N, Silva-Santos B. γδ T cells in tissue physiology and surveillance. Nat Rev Immunol. 2021; 21(4):221-232.
  7. Romero D. Immunotherapy: PD-1 says goodbye, TIM-3 says hello. Nat Rev Clin Oncol. 2016; 13(4):202-203.
  8. Rimmerman N, Verdiger H, Goldenberg H, Naggan L, Robinson E, Kozela E, et al. Microglia and their LAG3 checkpoint underlie the antidepressant and neurogenesis-enhancing effects of electroconvulsive stimulation. Mol Psychiatry. 2022; 27(2):1120-1135.
  9. Iadecola C, Buckwalter MS, Anrather J. Immune responses to stroke: mechanisms, modulation, and therapeutic potential. J Clin Invest. 2020; 130(6):2777-2788.
  10. Li S, Huang Y, Liu Y, Rocha M, Li X, Wei P, et al. Change and predictive ability of circulating immunoregulatory lymphocytes in long-term outcomes of acute ischemic stroke. J Cereb Blood Flow Metab. 2021; 41(9):2280-2294.
  11. Liesz A, Zhou W, Na SY, Hämmerling GJ, Garbi N, Karcher S, et al. Boosting regulatory T cells limits neuroinflammation in permanent cortical stroke. J Neurosci. 2013; 33(44):17350-17362.
  12. Westendorp WF, Dames C, Nederkoorn PJ, Meisel A. Immunodepression, Infections, and Functional Outcome in Ischemic Stroke. Stroke. 2022; 53(5):1438-1448.
  13. Fan KQ, Li YY, Wang HL, Mao XT, Guo JX, Wang F, et al. Stress-Induced Metabolic Disorder in Peripheral CD4+ T Cells Leads to Anxiety-like Behavior. Cell. 2019; 179(4):864-879.
  14. Zdanowicz N, Reynaert C, Jacques D, Dubois T. Depression and Immunity: a Psychosomatic Unit. Psychiatr Danub. 2017; 29(Suppl 3):274-278.
  15. Marazziti D, Torrigiani S, Carbone MG, Mucci F, Flamini W, Ivaldi T, et al. Neutrophil/Lymphocyte, Platelet/Lymphocyte, and Monocyte/Lymphocyte Ratios in Mood Disorders. Curr Med Chem. 2022; 29(36):5758-5781.
  16. Osborne LM, Gilden J, Kamperman AM, Hoogendijk WJG, Spicer J, Drexhage HA, et al. T-cell defects and postpartum depression. Brain Behav Immun. 2020; 87:397-403.
  17. Maqbool S, Ihtesham A, Langove MN, Jamal S, Jamal T, Safian HA. Neuro-dermatological association between psoriasis and depression: an immune-mediated inflammatory process validating skin-brain axis theory. AIMS Neurosci. 2021; 8(3):340-354.
  18. Lu J, Ma L, Jiang J, Huang B, Mou T, Huang T, et al. Linking peripheral CD8+ single-cell transcriptomic characteristics of mood disorders underlying with the pathological mechanism. Clin Transl Med. 2021; 11(7):e489.
  19. Wolf Y, Anderson AC, Kuchroo VK. TIM3 comes of age as an inhibitory receptor. Nat Rev Immunol. 2020; 20(3):173-185.
  20. Kataoka S, Manandhar P, Lee J, Workman CJ, Banerjee H, Szymczak-Workman AL, et al. The costimulatory activity of Tim-3 requires Akt and MAPK signaling and its recruitment to the immune synapse. Sci Signal. 2021; 14(687):eaba0717.
  21. Zhao J, Lei Z, Liu Y, Li B, Zhang L, Fang H, et al. Human pregnancy up-regulates Tim-3 in innate immune cells for systemic immunity. J Immunol. 2009; 182(10):6618-6624.
  22. Anderson AC, Anderson DE, Bregoli L, Hastings WD, Kassam N, Lei C, et al. Promotion of tissue inflammation by the immune receptor Tim-3 expressed on innate immune cells. Science. 2007; 318(5853):1141-1143.
  23. Zhong GS, Yang R, Cai RY, Xu ZS, Li JY, Li T, et al. Flow cytometric analysis of peripheral blood related immune cells and cytokines in patients with depression. Int J Clin Exp Med. 2018; 11(3):2812-2820.
  24. Wu W, Zheng YL, Tian LP, Lai JB, Hu CC, Zhang P, et al. Circulating T lymphocyte subsets, cytokines, and immune checkpoint inhibitors in patients with bipolar II or major depression: a preliminary study. Sci Rep. 2017; 7:40530.
  25. Liu J, Zhang S, Hu Y, Yang Z, Li J, Liu X, et al. Tarrgeting PD-1 and Tim-3 Pathways to Reverse CD8 T-Cell Exhaustion and Enhance Ex Vivo T-Cell Responses to Autologous Dendritic/Tumor Vaccines. J Immunother. 2016; 39(4):171-180.
  26. Zhu H, Hu S, Li Y, Sun Y, Xiong X, Hu X, et al. Interleukins and Ischemic Stroke. Front Immunol. 2022; 13:828447.
  27. Villa RF, Ferrari F, Moretti A. Post-stroke depression: Mechanisms and pharmacological treatment. Pharmacol Ther. 2018; 184:131-144.
  28. Na KS, Jung HY, Kim YK. The role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2014; 48:277-286.
  29. Park HJ, Shim HS, An K, Starkweather A, Kim KS, Shim I. IL-4 Inhibits IL-1β-Induced Depressive-Like Behavior and Central Neurotransmitter Alterations. Mediators Inflamm. 2015; 2015:941413.
  30. Dong Y, Wang X, Zhou Y, Zheng Q, Chen Z, Zhang H, et al. Hypothalamus-pituitary-adrenal axis imbalance and inflammation contribute to sex differences in separation- and restraint-induced depression. Horm Behav. 2020; 122:104741.
  31. Chen Y, Leon-Ponte M, Pingle SC, O'Connell PJ, Ahern GP. T lymphocytes possess the machinery for 5-HT synthesis, storage, degradation and release. Acta Physiol (Oxf). 2015; 213(4):860-867.
  32. Wang X, Li B, Kim YJ, Wang YC, Li Z, Yu J, et al. Targeting monoamine oxidase A for T cell-based cancer immunotherapy. Sci Immunol. 2021; 6(59):eabh2383.
  33. Dixon KO, Tabaka M, Schramm MA, Xiao S, Tang R, Dionne D, et al. TIM-3 restrains anti-tumour immunity by regulating inflammasome activation. Nature. 2021; 595(7865):101-106.
  34. Kitaoka S. Inflammation in the brain and periphery found in animal models of depression and its behavioral relevance. J Pharmacol Sci. 2022; 148(2):262-266.
  35. Ogłodek EA. The role of PON-1, GR, IL-18, and OxLDL in depression with and without posttraumatic stress disorder. Pharmacol Rep. 2017; 69(5):837-845.
  36. Zahrai A, Vahid-Ansari F, Daigle M, Albert PR. Fluoxetine-induced recovery of serotonin and norepinephrine projections in a mouse model of post-stroke depression. Transl Psychiatry. 2020; 10(1):334.
  37. Chollet F, Rigal J, Marque P, Barbieux-Guillot M, Raposo N, Fabry V, et al. Serotonin Selective Reuptake Inhibitors (SSRIs) and Stroke. Curr Neurol Neurosci Rep. 2018; 18(12):100.
  38. Wiener CD, Moreira FP, Portela LV, Strogulski NR, Lara DR, da Silva RA, et al. Interleukin-6 and Interleukin-10 in mood disorders: A population-based study. Psychiatry Res. 2019; 273:685-689.
  39. Chi CH, Huang YY, Ye SZ, Shao MM, Jiang MX, Yang MY, et al. Interleukin-10 level is associated with post-stroke depression in acute ischaemic stroke patients. J Affect Disord. 2021; 293:254-260.
Iranian Journal of Immunology
Volume 20, Issue 4
December 2023
Pages 427-437
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