Immunomodulatory Role and Therapeutic Potential of HLA-DR+ Regulatory T Cells in Systemic Lupus Erythematosus

被引：0
作者：
Zhang, Jing [1 ]
Liao, Bei [1 ]
Wang, Xiaobing [1 ]
Liu, Weijun [1 ]
机构：
[1] Nanchang Univ, Candidate Branch Natl Clin Res Ctr Skin Dis, JXHC Key Lab Skin Infect & Immun, Affiliated Dermatol Hosp,Dermatol Hosp Jiangxi Pro, 388 Yingbingbei Rd, Nanchang 330003, Jiangxi, Peoples R China
来源：
IMMUNOLOGICAL INVESTIGATIONS | 2025年
关键词：
HLA-DR+ regulatory T cells; immune tolerance; systemic lupus erythematosus; ACTIVATION; EXPRESSION; RISK; TREG;
D O I：
10.1080/08820139.2025.2475816
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Background Systemic lupus erythematosus (SLE) is a complex autoimmune disease that affects multiple organ systems. A key element in maintaining immune tolerance and preventing autoimmunity is the role of regulatory T cells (Treg cells). Among these, HLA-DR+ Treg cells represent a distinct subset, and their altered expression and functionality in SLE are closely associated with the progression of the disease. This review explores the biological characteristics of HLA-DR+ Treg cells, their mechanisms of action in SLE, as well as their potential and the challenges they pose as therapeutic targets. Methods and results This review offers a comprehensive analysis of the mechanisms by which HLA-DR+ Treg cells regulate immune responses. It highlights their direct interactions with autoreactive T cells and antigen-presenting cells, which contribute to the suppression of autoimmunity. Additionally, the review explores the critical role of these cells in maintaining immune tolerance and their promising potential in the context of antigen-specific immunotherapy. Discussion The potential of HLA-DR+ Treg cells in the treatment of systemic lupus erythematosus (SLE) is considerable, particularly due to their capacity to generate antigen-specific Tregs. The development of Treg-based therapies, including the expansion of both polyclonal and antigen-specific Tregs, is an area of active investigation. Nonetheless, several challenges persist, such as the need to optimize protocols for Treg generation and expansion, ensure the stability of the Treg phenotype, and address potential safety concerns associated with cellular therapies.Continued research is essential to fully harness the potential of HLA-DR+ Treg cells in the treatment of SLE and other autoimmune diseases.
引用
收藏
页数：18
相关论文
共 94 条
  • [1] Acharya C., Magnusson M.O., Vajjah P., Oliver R., Zamacona M., Population pharmacokinetics and exposure-response for dapirolizumab pegol from a phase 2b trial in patients with systemic lupus erythematosus, The Journal of Clinical Pharmacology, 63, 4, pp. 435-444, (2023)
  • [2] Ahmed A., Adiga V., Nayak S., Uday Kumar J.A.J., Dhar C., Sahoo P.N., Sundararaj B.K., Souza G.D., Vyakarnam A., Circulating HLA-DR+CD4+ effector memory T cells resistant to CCR5 and PD-L1 mediated suppression compromise regulatory T cell function in tuberculosis, PLOS Pathogens, 14, 9, (2018)
  • [3] Apostolidis S.A., Rodriguez-Rodriguez N., Suarez-Fueyo A., Dioufa N., Ozcan E., Crispin J.C., Tsokos M.G., Tsokos G.C., Phosphatase PP2A is requisite for the function of regulatory T cells, Nature Immunology, 17, 5, pp. 556-564, (2016)
  • [4] Barber M.R.W., Drenkard C., Falasinnu T., Hoi A., Mak A., Kow N.Y., Svenungsson E., Peterson J., Clarke A.E., Ramsey-Goldman R., Global epidemiology of systemic lupus erythematosus, Nature Reviews Rheumatology, 17, 9, pp. 515-532, (2021)
  • [5] Basta F., Fasola F., Triantafyllias K., Schwarting A., Systemic Lupus Erythematosus (SLE) therapy: The old and the new, Rheumatology and Therapy, 7, 3, pp. 433-446, (2020)
  • [6] Blinova V.G., Zhdanov D.D., Many faces of regulatory T cells: Heterogeneity or plasticity?, Cells, 13, 11, (2024)
  • [7] Bonelli M., Savitskaya A., von Dalwigk K., Steiner C.W., Aletaha D., Smolen J.S., Scheinecker C., Quantitative and qualitative deficiencies of regulatory T cells in patients with systemic lupus erythematosus (SLE), International Immunology, 20, 7, pp. 861-868, (2008)
  • [8] Bui Q.T., Wilensky R.L., Darapladib, Expert Opinion on Investigational Drugs, 19, 1, pp. 161-168, (2010)
  • [9] Caulfield A.J., Lathem W.W., Heitman J., Disruption of fas-fas ligand signaling, apoptosis, and innate immunity by bacterial pathogens, PLOS Pathogens, 10, 8, (2014)
  • [10] Cencioni M.T., Santini S., Ruocco G., Borsellino G., De Bardi M., Grasso M.G., Ruggieri S., Gasperini C., Centonze D., Barila D., Battistini L., Volpe E., Fas-ligand regulates differential activation-induced cell death of human T-helper 1 and 17 cells in healthy donors and multiple sclerosis patients, Cell Death Dis, 6, (2015)
12345678910