内质网磷酸化修饰与肺结核感染后免疫反应的相关性研究

doi:10.3969/j.issn.1006-6233.2024.02.08

Abstract
Figure/Table
References
Related Citation (15)

Download: PDF (1935 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

Abstract Objective: To observe the correlation between phosphorylation of endoplasmic reticulum (ER) and immune response after pulmonary tuberculosis infection. Methods: In this observational study, we recruited adult tuberculosis patients (n=19) who were treated in our hospital from January 2021 to June 2023 and family contacts (healthy contacts) who had no symptoms of tuberculosis (n=20). Blood samples were collected from all patients before treatment, and the characteristics of specific T cell response, cytokine production and expression of phosphorylated protein kinase-like endoplasmic reticulum kinase (PERK) and activator of transcription 3(STAT3) of Mycobacterium tuberculosis were analyzed. Results: Compared with healthy contacts, the levels of IL-17 and IL-22 in whole blood samples stimulated by PPD in tuberculosis patients decreased significantly (P<0.05), and the levels of IL-6 and IL-10 increased significantly (P<0.05). Compared with healthy contacts, the spontaneous concentrations of IL-10, IL-6 and IFN-γ in tuberculosis patients were higher (P<0.05). In the absence of IL-6 stimulation in vitro, the level of PERK in CD4⁺ T cells of tuberculosis patients was significantly higher than that of healthy contacts (P<0.001). Adding IL-6 led to a significant increase in the level of PERK in CD4⁺ T cells of healthy contacts compared with those without IL-6 stimulation in vitro (P<0.01). Compared with healthy contacts, CD4⁺ T cells of tuberculosis patients had higher expression of STAT3 protein (P<0.05). In all donors and tuberculosis patients, there was a significant positive correlation between the expression of PERK and STAT3 in CD4⁺ T cells (rho=0.571, 0.503, all P<0.05). The ratio of CD40L/IL-2 co-expressing T cells and CD40L/IFN-γ co-expressing T cells was negatively correlated with STAT3 expression only in tuberculosis patients (rho = -0.481, -0.705, P=0.032, <0.001). Conclusion: This study provides evidence that the PERK/STAT3 signaling pathway related to ER phosphorylation modification may drive the immunosuppressive/antiproliferative T cell response in tuberculosis patients.

Key words： Endoplasmic reticulum T cells Pulmonary tuberculosis Phosphorylated protein kinase-like endoplasmic reticulum kinase Immune response

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors

Cite this article:

URL:

http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2024.02.08 OR http://www.hbyxzzs.cn/EN/Y2024/V30/I2/218

[1] Ravesloot-chavez M M,Van Dis E,Stanley S A.The innate immune response to Mycobacterium tuberculosis infection[J].Annu Rev Immunol,2021,(39):611-637.
[2] Morrison H,McShane H.Local pulmonary immunological biomarkers in tuberculosis[J].Front Immunol,2021,(12):640916.
[3] Queiroz M A F,Lima S S,Amoras E S G,et al.Epidemiological and cytokine profile of patients with pulmonary and extrapulmonary tuberculosis in a population of the brazilian amazon[J].Microorganisms,2022,10(10):2075.
[4] Lungu P,Mushota K,Njelesani E,et al.Expression of mycobacterium tuberculosis induced STAT3 and STAT3 and the implications on innate immunity in TB patients vs healthy contacts in high TB/HIV endemic setting:A cross-sectional analytical study[J].Plos One,2022,17(7):263624.
[5] Lu G,Li Q,Liu J,et al.Inhibition of endoplasmic reticulum stress and the downstream pathways protects CD4⁺ T cells against apoptosis and immune dysregulation in sepsis[J].IUBMB life,2022,74(11):1070-1080.
[6] Chen X,Cubillos-ruiz J R.Endoplasmic reticulum stress signals in the tumour and its microenvironment[J].Nat Rev Cancer,2021,21(2):71-88.
[7] Wang J L,Liu H,Jing Z C,et al.18β-Glycyrrhetinic acid ameliorates endoplasmic reticulum stress-induced inflammation in pulmonary arterial hypertension through PERK/eIF2α/NF-κB signaling[J].Chinese Journal of Physiology,2022,65(4):187.
[8] Difrancesco A M,Verrecchia E,Manna S,et al.The chitinases as biomarkers in immune-mediate diseases[J].Clin Chem Lab Med,2023,61(8):1363-1381.
[9] Froes JR L A R,Trindade M A B,Sotto M N.Immunology of leprosy[J].Int Rev Immunol,2022,41(2):72-83.
[10] Kumar N,Khan N,Cleveland D,et al.A common approach for fighting tuberculosis and leprosy:controlling endoplasmic reticulum stress in myeloid-derived suppressor cells[J].Immunotherapy,2021,13(18):1555-1563.
[11] Keeely-scumpia K M,Choi A,Shirazi R,et al.ER stress regulates immunosuppressive function of myeloid derived suppressor cells in leprosy that can be overcome in the presence of IFN-γ[J].Iscience,2020,23(5):101050.
[12] Lou X,Gao D,Yang L,et al.Endoplasmic reticulum stress mediates the myeloid-derived immune suppression associated with cancer and infectious disease[J].Transl Med,2023,21(1):1.
[13] Li H,Tsokos G C.IL-23/IL-17 axis in inflammatory rheumatic diseases[J].Clin Rev Allergy Immunol,2021,60(1):31-45.
[14] Lungu P,Mushota K,Njelesani E,et al.Expression of mycobacterium tuberculosis induced SOCS3 and STAT3 and the implications on innate immunity in TB patients vs healthy contacts in high TB/HIV endemic setting:a cross-sectional analytical study[J].Plos One,2022,17(7):e0263624.
[15] Queiroz M A F,Lima S S,Amoras E S G,et al.Epidemiological and cytokine profile of patients with pulmonary and extrapulmonary tuberculosis in a population of the brazilian amazon[J].Microorganisms,2022,10(10):2075.
[16] Yan S,Golumba-negy V,Kotschenreuther K,et al.Membrane-bound IL-6R is upregulated on Th17 cells and inhibits Treg cell migration by regulating post-translational modification of VASP in autoimmune arthritis[J].Cell Mol Life Sci,2022,79(1):3.