Skip to main content

Advertisement

SpringerLink
Log in

JKAP, Th1 cells, and Th17 cells are dysregulated and inter-correlated, among them JKAP and Th17 cells relate to cognitive impairment progression in Alzheimer’s disease patients

  • Original Article
  • Published:
Irish Journal of Medical Science (1971 -) Aims and scope Submit manuscript

Abstract

Background

JNK pathway-associated phosphatase (JKAP) is engaged in Alzheimer’s disease (AD) pathology via regulating immune response, cluster of differentiation 4 positive (CD4+) T cell differentiation, inflammation, and phosphorylated tau (p-tau). This study aimed to investigate its clinical value serving as a biomarker for AD.

Methods

Fifty AD patients, 50 Parkinson’s disease (PD) patients, and 50 controls (patients with non-degenerative neurological diseases with normal cognition) were enrolled. Their β-protein 42 (Aβ42), total tau (t-tau), p-tau, and Mini-Mental State Examination (MMSE) scale were assessed. Furthermore, JKAP in serum and T-help type 1 (Th1) and T-help type 17 (Th17) cells in CD4+ T cells were measured.

Results

JKAP level was lower, while Th17 cell proportion (but not Th1 cell proportion) was higher in AD patients compared with PD patients and controls (all P < 0.01). Besides, JKAP level negatively correlated with both Th1 (r =  − 0.306, P = 0.030) and Th17 (r =  − 0.380, P = 0.006) cell proportions in AD patients but not PD patients and controls. Furthermore, in AD patients, JKAP positively correlated with Aβ42 (r = 0.307, P = 0.030) and MMSE score (r = 0.350, P = 0.013) while negatively correlated with p-tau (r =  − 0.280, P = 0.048); Th17 cell proportion negatively associated with Aβ42 (r =  − 0.281, P = 0.048) and MMSE score (r =  − 0.366, P = 0.009). Notably, JKAP was negatively related to 1-year (r =  − 0.297, P = 0.038) and 2-year MMSE decline (r =  − 0.304, P = 0.048); Th17 cell proportion was positively linked with 1-year (r = 0.392; P = 0.008), 2-year (r = 0.482, P = 0.001), and 3-year (r = 0.365, P = 0.013) MMSE decline.

Conclusion

JKAP, Th1 cells, and Th17 cells are dysregulated and inter-correlated; among them, JKAP and Th17 cells relate to cognitive impairment progression in AD patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Winblad B, Amouyel P, Andrieu S et al (2016) Defeating Alzheimer’s disease and other dementias: a priority for European science and society. Lancet Neurol 15(5):455–532

    Article  Google Scholar 

  2. Tiwari S, Atluri V, Kaushik A et al (2019) Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics. Int J Nanomedicine 14:5541–5554

    Article  CAS  Google Scholar 

  3. Yu JT, Xu W, Tan CC et al (2020) Evidence-based prevention of Alzheimer’s disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials. J Neurol Neurosurg Psychiatry 91(11):1201–1209

    Article  Google Scholar 

  4. Gaugler JE, Yu F, Davila HW, Shippee T (2014) Alzheimer’s disease and nursing homes. Health Aff (Millwood) 33(4):650–657

    Article  Google Scholar 

  5. Weller J, Budson A (2018) Current understanding of Alzheimer's disease diagnosis and treatment. F1000Res 7

  6. Monsonego A, Nemirovsky A, Harpaz I (2013) CD4 T cells in immunity and immunotherapy of Alzheimer’s disease. Immunology 139(4):438–446

    Article  CAS  Google Scholar 

  7. Chuang HC, Tan TH (2019) MAP4K family kinases and DUSP Family phosphatases in T-cell signaling and systemic lupus erythematosus. Cells 8(11)

  8. Yu D, Peng X, Li P (2020) The correlation between Jun N-terminal kinase pathway-associated phosphatase and Th1 cell or Th17 cell in sepsis and their potential roles in clinical sepsis management. Ir J Med Sci

  9. Chuang HC, Chen YM, Hung WT et al (2016) Downregulation of the phosphatase JKAP/DUSP22 in T cells as a potential new biomarker of systemic lupus erythematosus nephritis. Oncotarget 7(36):57593–57605

    Article  Google Scholar 

  10. Zhou R, Chang Y, Liu J et al (2017) JNK pathway-associated phosphatase/DUSP22 suppresses CD4(+) T-cell activation and Th1/Th17-cell differentiation and negatively correlates with clinical activity in inflammatory bowel disease. Front Immunol 8:781

    Article  Google Scholar 

  11. Kubick N, Flournoy PCH, Enciu AM et al (2020) Drugs modulating CD4+ T cells blood-brain barrier interaction in Alzheimer's disease. Pharmaceutics 12(9)

  12. Terzioglu G, Ormeci B, Turksoy O et al (2017) Mitochondrial depletion in CD4(+) and CD19(+) peripheral lymphocytes in early stage Alzheimer’s disease. Mech Ageing Dev 167:24–29

    Article  CAS  Google Scholar 

  13. Mittal K, Eremenko E, Berner O et al (2019) CD4 T cells induce a subset of MHCII-Expressing microglia that attenuates alzheimer pathology. iScience 16:298–311

  14. Saresella M, Calabrese E, Marventano I et al (2011) Increased activity of Th-17 and Th-9 lymphocytes and a skewing of the post-thymic differentiation pathway are seen in Alzheimer’s disease. Brain Behav Immun 25(3):539–547

    Article  CAS  Google Scholar 

  15. Jack CR Jr, Albert MS, Knopman DS et al (2011) Introduction to the recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7(3):257–262

    Article  Google Scholar 

  16. Berardelli A, Wenning GK, Antonini A et al (2013) EFNS/MDS-ES/ENS [corrected] recommendations for the diagnosis of Parkinson’s disease. Eur J Neurol 20(1):16–34

    Article  CAS  Google Scholar 

  17. Cumming TB, Churilov L, Linden T, Bernhardt J (2013) Montreal cognitive assessment and mini-mental state examination are both valid cognitive tools in stroke. Acta Neurol Scand 128(2):122–129

    Article  CAS  Google Scholar 

  18. Sanchez-Mut JV, Aso E, Heyn H et al (2014) Promoter hypermethylation of the phosphatase DUSP22 mediates PKA-dependent TAU phosphorylation and CREB activation in Alzheimer’s disease. Hippocampus 24(4):363–368

    Article  CAS  Google Scholar 

  19. Ciccocioppo F, Lanuti P, Pierdomenico L et al (2019) The characterization of regulatory t-cell profiles in Alzheimer’s disease and multiple sclerosis. Sci Rep 9(1):8788

    Article  Google Scholar 

  20. Monteiro FA, Sousa MM, Cardoso I et al (2006) Activation of ERK1/2 MAP kinases in familial amyloidotic polyneuropathy. J Neurochem 97(1):151–161

    Article  CAS  Google Scholar 

  21. Banzhaf-Strathmann J, Benito E, May S et al (2014) MicroRNA-125b induces tau hyperphosphorylation and cognitive deficits in Alzheimer’s disease. EMBO J 33(15):1667–1680

    Article  CAS  Google Scholar 

  22. Marsh SE, Abud EM, Lakatos A et al (2016) The adaptive immune system restrains Alzheimer’s disease pathogenesis by modulating microglial function. Proc Natl Acad Sci U S A 113(9):E1316-1325

    Article  CAS  Google Scholar 

  23. Kisler K, Nelson AR, Montagne A, Zlokovic BV (2017) Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease. Nat Rev Neurosci 18(7):419–434

    Article  CAS  Google Scholar 

  24. Chen X, Hu Y, Cao Z, Liu Q et al (2018) Cerebrospinal fluid inflammatory cytokine aberrations in Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis: a systematic review and meta-analysis. Front Immunol 9:2122

    Article  Google Scholar 

  25. Chen J, Liu X, Zhong Y (2020) Interleukin-17A: the key cytokine in neurodegenerative diseases. Front Aging Neurosci 12:566922

  26. Faraco G, Brea D, Garcia-Bonilla L et al (2018) Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response. Nat Neurosci 21(2):240–249

    Article  CAS  Google Scholar 

  27. Perez-Sen R, Queipo MJ, Gil-Redondo JC et al (2019) Dual-specificity phosphatase regulation in neurons and glial cells. Int J Mol Sci 20(8)

  28. Queipo MJ, Gil-Redondo JC, Morente V et al (2017) P2X7 Nucleotide and EGF receptors exert dual modulation of the dual-specificity phosphatase 6 (MKP-3) in granule neurons and astrocytes, contributing to negative feedback on erk signaling. Front Mol Neurosci 10:448

    Article  Google Scholar 

Download references

Author information

Author notes

  1. Junyan Zeng and Jie Liu contributed equally

Authors and Affiliations

  1. Department of Neurology, Dongpo District, Meishan Cardio Cerebrovascular Disease Hospital, No.66, West Third Section of Qitong Road, Meishan, 620010, China

    Junyan Zeng, Xiongfei Zhao & Jie Zhang

  2. Department of Neurology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, China

    Jie Liu & Qiumin Qu

Authors
  1. Junyan Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jie Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qiumin Qu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiongfei Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jie Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Xiongfei Zhao or Jie Zhang.

Ethics declarations

Ethics approval

The ethic approval from the Institutional Review Board was acquired before initiation of study, and the written informed consent was obtained from each enrolled subject.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zeng, J., Liu, J., Qu, Q. et al. JKAP, Th1 cells, and Th17 cells are dysregulated and inter-correlated, among them JKAP and Th17 cells relate to cognitive impairment progression in Alzheimer’s disease patients. Ir J Med Sci 191, 1855–1861 (2022). https://doi.org/10.1007/s11845-021-02749-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11845-021-02749-2

Keywords

Search

Navigation