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

Abstract

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.