Th1, Th17, and Treg Responses are Differently Modulated by TNF-α Inhibitors and Methotrexate in Psoriasis Patients

Abstract

Psoriasis is a chronic, recurrent, immune-mediated, hyperproliferative inflammatory skin disease. The role of the adaptive immune system, particularly of Th1 and Th17 lymphocytes, has been regarded as prominent in the immunopathogenesis of psoriasis, as well as decreased Tregs function. Immunobiological drugs were administered in therapeutic pulses and a few studies evaluate their effects on the immune repertoire. The aim of this study was to evaluate the adaptive immune profile of patients with severe psoriasis under immunobiological treatment in two time points. Thirty-two psoriasis patients and 10 control patients were evaluated. In the group of psoriasis patients, 10 patients were on anti-TNF and 14 patients on methotrexate treatment, while 8 individuals were not treated. IL-17, IFN-γ, TNF-α, IL-6, IL-2, and IL-10 were analyzed. CD4 T cell intracellular cytokines were analyzed. It was observed that stimulation could significantly increase the production of IL-17, IFN-γ, TNF-α, and IL-10 only before anti-TNF pulse therapy. The activation of Th1 and Treg cells after stimulation was significantly higher before anti-TNF pulse. Patients on methotrexate or anti-TNF therapy produced significantly lower levels of TNF-α, IL-10, and IL-6. Furthermore, these patients showed a significant decrease in the activated CD4+ T cells. The treatment with immunomodulator or methotrexate modulates the activation of CD4+ T cells, and anti-TNF treatment appears to have a modulating effect on the activation and production of Th1, Th17, and Treg cells.

Immune Regulation of TNFAIP3 in Psoriasis through Its Association with Th1 and Th17 Cell Differentiation and p38 Activation

“…Previous studies reported that Th1 and Th17 cells have critical roles in the pathogenesis of psoriasis [16]. Inflammatory cytokines, including IL-17, IFN-γ, and TNFα, are also involved in the inflammatory process of psoriasis [17]. Taken together, the pathogenesis of psoriasis involves complicated immune regulation with Th1 and Th17 dysregulation.…”

“…It was previously demonstrated that TNF-α antagonists have high efficacy for the treatment of psoriasis by inhibiting the inflammation cascade triggered by TNF-α [25]. Studies also reported that anti-TNF therapy interfered with immune responses to modulate the productions of IFN-γ, TNF-α, and IL-17A [17]. However, the exact mechanisms involved in the effects of pathogenic cytokines in psoriasis and antipsoriatic treatment with TNF-α antagonists remain unclear.…”

Interleukin-17 cytokines: Effectors and targets in psoriasis—A breakthrough in understanding and treatment

“…Apart from therapeutics with a direct effect on IL-17 family members, there is accumulating evidence for a reduction of lesional IL-17 levels with known systemic drugs for plaque psoriasis including methotrexate (Furiati et al, 2019;Reich et al, 2019a).…”

Serum Fatty Acid Binding Protein 5 (FABP5) as a Potential Biomarker of Inflammation in Psoriasis.

“…Higher serum concentration of FABP5 in our study may re ect its epidermal level. The underlying mechanism of the association of FABP5 and psoriasis is not clear yet, but one of the possible explanation is role of the adaptive immune system, particularly of Th1 and Th17 lymphocytes, which has been regarded as prominent in the immunopathogenesis of psoriasis [19]. Interestingly, studies have shown that FABP5 can increase Th17-cell differentiation [20] and aberrant FABP5 activity may over activate immune cells leading to in ammatory autoimmune diseases [21].…”