Background Psoriasis arthritis is one of chronic, relapsing, inflammatory autoimmune disorders with skin lesions and joint damage. A therapeutic revolution of psoriatic arthritis (PsA) is still a considerable unmet need in the past decades. It has been well known that the imbalance of Th17 cells and regulatory T cells (Tregs) may be a pivotal cause of PsA. Correction of this dysfunction can be a potential therapy of PsA.
Objectives In this study, we measured and compared both absolute numbers and proportions of CD4+CD17+ Th17 cells and CD4+CD25+Foxp3+ Treg cells in peripheral blood of PsA patients and healthy controls to explore the immunopathogenesis of PsA; on the other hand, the effects of low-dose recombinant human IL-2 (rhIL-2) on Th17 and Treg cells were investigated in patients with PsA.
Methods Both absolute numbers and proportions of Treg and Th17 cells in peripheral blood, defined as the CD4+CD25+Foxp3+T or CD4+IL-17+ T cell populations, were examined by flow cytometry in 40 healthy controls and 77 patients with PsA, including 39 patients who had never received disease-modifying antirheumatic drugs (DMARDs) and 38 patients who were receiving or had received DMARDs. Among these patients, 20 patients consented at enrollment to receive rhIL-2 treatment. Before and after treatment (50WIU/d for 5 days, IH), Th17 and Treg cells in peripheral blood were analyzed by flow cytometry.
Results The absolute count of Th17 cells in patients with PsA was very significantly higher than that of healthy controls (P<0.01), but the proportions of Th17 cell were not seen difference between PsA and healthy controls (P>0.05). In contrast with treated-PsA patients, the absolute count of Th17 cells was significant higher in untreated-PsA patients (P<0.05). After the course of rhIL-2 treatment, there was a significant increase in the absolute count of Treg cells (P<0.05), but no diference in the absolute count of Th17 cells, Th17/Treg was significantly lower and went back to nomal.
Conclusions The results suggest that, not the proportion, but the decrease in the absolute count of Th17 cells, defined as the CD4+CD17+ populations, contributes to the pathogenesis of PsA. After the treatment of rhIL-2, there was a more significant increase in the absolute count of Treg cells than that of Th17, and consequently the balance of Th17/Treg was restored to normal, leading to the development of new therapies.
Karczewski J, Dobrowolska A, Rychlewskahańczewska A, et al. New insights into the role of T cells in pathogenesis of psoriasis and psoriatic arthritis[J]. Autoimmunity, 2016:1.DOI:10.3109/08916934.2016.1166214.
Yoo I S, Lee J H, Song S T, et al. T-helper 17 cells: the driving force of psoriasis and psoriatic arthritis.[J]. International Journal of Rheumatic Diseases, 2012, 15(6):531–537. DOI:10.1111/j.1756–185X.2012.01813.x.
Szodoray P, Nakken B, Barath S, et al. Altered Th17 cells and Th17/regulatory T-cell ratios indicate the subsequent conversion from undifferentiated connective tissue disease to definitive systemic autoimmune disorders[J]. Human Immunology, 2013, 74(12):1510–8. DOI:10.1016/j.humimm.2013.08.003.
Raychaudhuri S P. Role of IL-17 in psoriasis and psoriatic arthritis.[J]. Clinical Reviews in Allergy & Immunology, 2013, 44(2):183–193. DOI: 10.1007/s12016–012–8307–1.
Disclosure of Interest None declared