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.
Highlights
Www.nature.com/scientificreports being activated by these cytokines, myeloid DCs have TLRs (Toll-like receptors), through which they can directly interact with the auto-RNA–LL-37 complex, causing their concomitant activation, starting to produce several proinflammatory cytokines (IL-23, TNF-α, IL-12, IL-6, IL-20, and IL-1)[11]
IL-17, IFN-γ, TNF-α, IL-10, IL-6, and IL-2 levels were analyzed by cytometric bead array (CBA) of the Peripheral blood mononuclear cells (PBMCs) culture supernatant 48 h after stimulation with anti-CD3 and anti-CD28 or after no stimulation (Fig. 1)
Analysis of IL-17 levels in the PBMC supernatants showed that anti-CD3 and anti-CD28 stimulation significantly increased IL-17 production just before the pulse therapy, compared to the untreated supernatants (p = 0.031) (Fig. 1A)
Summary
Www.nature.com/scientificreports being activated by these cytokines, myeloid DCs have TLRs (Toll-like receptors), through which they can directly interact with the auto-RNA–LL-37 complex, causing their concomitant activation, starting to produce several proinflammatory cytokines (IL-23, TNF-α, IL-12, IL-6, IL-20, and IL-1)[11]. Keratinocytes are the main targets of these cytokines, especially of IL-17, IFN-γ, TNF-α, and IL-22, which directly or indirectly lead to their hyperproliferation, as well as induce them to produce various other cytokines, chemokines, and antimicrobial peptide, which in turn continue to stimulate the activation and recruitment of cells of the innate and adaptive immune system to the lesions, perpetuating the inflammatory process of psoriasis[9]. Regulatory T cells (Tregs), identified as CD4+ CD25+ Foxp3+ cells, play a crucial role in immune tissue homeostasis and in self-tolerance because they are capable of suppressing effector cell activation and proliferation through the production of IL-10, controlling inflammatory processes in the body[21]. Ustekinumab is an inhibitor of IL-23, and secukinumab is an inhibitor of IL-17A34
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