Altered immunoregulation in rheumatoid arthritis: the role of regulatory T cells and proinflammatory Th17 cells and therapeutic implications.

Alessia Alunno,Riccardo Terenzi,Sara Caterbi,Mirko Manetti,Lidia Ibba-Manneschi,Onelia Bistoni,Roberto Gerli,Elena Bartoloni,Valentina Valentini

doi:10.1155/2015/751793

Alessia Alunno, Riccardo Terenzi + Show 7 more

Open Access

https://doi.org/10.1155/2015/751793

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Abstract

In recent years several studies investigated the role of T lymphocyte subpopulations in the pathogenesis of rheumatoid arthritis (RA). Pathogenic Th17 cells mediate pannus growth, osteoclastogenesis, and synovial neoangiogenesis; hence they are key players in the development of the disease. On the other hand, regulatory T (Treg) cells are a T cell subset whose peculiar function is to suppress autoreactive lymphocytes. The imbalance between Th17 and Treg cells has been identified as a crucial event in the pathogenesis of RA. In addition, the effects of currently employed RA therapeutic strategies on these lymphocyte subpopulations have been extensively investigated. This review article aims to discuss current knowledge on Treg and Th17 cells in RA and possible implications of their therapeutic targeting in this disorder.

Highlights

Rheumatoid arthritis (RA) is a chronic inflammatory condition characterized by progressive articular cartilage destruction and bone resorption [1]
The aim of this paper is the critical discussion of current knowledge on Treg and Th17 cells in RA and possible implications of their therapeutic targeting in this disorder
We reported that IL-17-producing CD3+CD4−CD8− double negative T cells isolated from primary Sjogren syndrome (pSS) patients, but not those from healthy subjects, are insensitive to dexamethasone in vitro [83]

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory condition characterized by progressive articular cartilage destruction and bone resorption [1]. Th1 and Th2 cells mediate immune responses against intracellular and extracellular pathogens, respectively Both cell subsets may participate in the development of autoimmunity, and Th2 cells are involved in allergy and asthma. Th17 cells are normally responsible for immune responses against extracellular bacteria and fungi but are leading actors in the autoimmunity scenario, while Treg cells mediate immune tolerance and attempt to maintain lymphocyte homeostasis. Their opposite behavior as well as their reciprocal plasticity pointed out the importance of Th17/Treg cell imbalance in the pathogenesis of RA. The aim of this paper is the critical discussion of current knowledge on Treg and Th17 cells in RA and possible implications of their therapeutic targeting in this disorder

Treg Cells in RA Peripheral Blood and Synovium

Proinflammatory Th17 Cells in RA Peripheral Blood and Synovium

The Effects of Different RA Therapeutic Approaches on Treg and Th17 Cells

Conclusions