CD4⁺CD25⁺ regulatory T cells in systemic sclerosis and other rheumatic diseases

Abstract

Systemic sclerosis (SSc) is a generalized connective tissue disorder, characterized by a wide spectrum of microvascular and immunological abnormalities, leading to a progressive thickening and fibrosis of the skin and other organs, such as the lungs, GI tract, heart and kidneys. SSc is thought to be an autoimmune disease owing to the presence of high affinity antibodies and possible clinical overlap with other autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Autoimmune diseases arise because of a breakdown in immunological self tolerance. Self tolerance is maintained via multiple regulatory mechanisms within the immune system, including the thymic deletion of self-reactive T cells and mechanisms of peripheral tolerance. In recent years, the presence of CD4⁺CD25⁺FOXP3⁺ Tregs has been identified as a major mechanism of peripheral tolerance, and accumulating evidence indicates that alterations in Treg frequencies and/or function may contribute to autoimmune diseases. Here, we will review recent data on the percentage, function and phenotype of CD4⁺CD25⁺ Tregs in rheumatic disease, and discuss how recent developments may guide research in this area in SSc.

Keywords::

• FOXP3
• immune regulation
• regulatory T cells
• rheumatoid arthritis
• scleroderma
• systemic sclerosis
• TGF-β
• Th17
• Treg

Financial & competing interests disclosure

The laboratory of Leonie S Taams is in part supported by financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust. Gina J Walter is supported by a PhD studentship from Arthritis Research UK (ref. #19307). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.