Elsevier

Autoimmunity Reviews

Volume 14, Issue 4, April 2015, Pages 286-292
Autoimmunity Reviews

Review
T cell responses in psoriasis and psoriatic arthritis

https://doi.org/10.1016/j.autrev.2014.11.012Get rights and content

Abstract

According to the current view the histological features of psoriasis arise as a consequence of the interplay between T cells, dendritic cells and keratinocytes giving rise to a self-perpetuating loop that amplifies and sustains inflammation in lesional skin. In particular, myeloid dendritic cell secretion of IL-23 and IL-12 activates IL-17-producing T cells, Th22 and Th1 cells, leading to the production of inflammatory cytokines such as IL-17, IFN-γ, TNF and IL-22. These cytokines mediate effects on keratinocytes thus establishing the inflammatory loop.

Unlike psoriasis the immunopathogenic features of psoriatic arthritis are poorly characterized and there is a gap in the knowledge of the pathogenic link between inflammatory T cell responses arising in the skin and the development of joint inflammation.

Here we review the knowledge accumulated over the years from the early evidence of autoreactive CD8 T cells that was studied mainly in the years 1990s and 2000s to the recent findings of the role of Th17, Tc17 cells and γδ T cells in psoriatic disease pathogenesis. The review will also focus on common and distinguishing features of T cell responses in psoriatic plaques and in synovial fluid of patients with psoriatic arthritis.

The integration of this information could help to distinguish the role played by T cells in the initiation phase of the disease from the role of T cells as downstream effectors sustaining inflammation in psoriatic plaques and potentially leading to disease manifestation in distant joints.

Section snippets

Psoriasis and psoriatic arthritis clinical features

Psoriasis is a chronic inflammatory skin disease affecting approximately 2%–4% of the population worldwide and is considered the most prevalent immune-mediated disease in humans. [1]. Plaque psoriasis, also known as psoriasis vulgaris, is the commonest form of the disease, representing almost 90% of psoriatic patients [2]. The lesions are characterized by erythematous dry, sharply demarcated plaques with loosely adherent silvery white scalest. The disease appears in other different clinical

Pathogenesis of psoriasis and psoriatic arthritis

An important distinction has been recently made in psoriasis natural history by identifying 2 phases: an initiation phase that starts inflammation and a maintenance phase that perpetuates the inflammatory state [23]. This conceptual distinction can help to divide the cellular and molecular events that determine triggering of the disease from those that are the results of the self-perpetuating cycle and represent downstream effector arms of the inflammatory process.

Psoriasis lesions are

Antigen-specific responses in psoriasis and psoriatic arthritis

The question of antigen specificity of T cell responses in psoriasis and psoriatic arthritis is still unanswered and is strongly linked the autoimmune nature of the disease [53].

An association between streptococcal throat infection and the acute guttate form of psoriasis (an early onset form) has been demonstrated in many studies, and the reported incidence of streptococcal infections preceding this type of psoriasis ranges between 56% and 97% [5].

Chronic plaque psoriasis is also exacerbated

Concluding remarks

The triggering event of the initial phase of the disease is unclear as the autoimmune etiology of psoriasis is unclear. By integrating information on recent advances on Th17/Th1 γδT cell contribution in determining inflammation on psoriatic skin together with early data on keratin cross-reactive CD8 T cells with specificity for streptococcal antigens, we have highlighted the role of the different subpopulations of T cells in psoriasis and psoriatic arthritis and hypothesized a hierarchical role

Take-home messages

  • Keratin cross-reactive CD8 T cells with specificity for microbial antigens can represent the core autoimmune mechanism of psoriasis pathogenesis.

  • Th17 T cells and γδ T cells act as downstream effectors stimulated by common-antigens or bystander activation

  • Th17 driven inflammatory cycle can lead to the main clinical manifestations in the skin and extend inflammation to the joint.

  • Dendritic cells in genetically predisposed individuals could cross-present self-epitopes leading to epitope spreading in

Acknowledgments

We thank Prof. Giuseppe Banfi, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milan (Italy); Dr. Daniela Talarico, S. Raffaele Research Hospital, Milan (Italy) and Prof. Riccardo Gavioli, University of Ferrara, Ferrara (Italy) for critical reading of the manuscript. This work received support from National Psoriasis Foundation.

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