Effect of methotrexate monotherapy on T‐cell subsets in the peripheral circulation in psoriasis

Abstract

Background. Psoriasis is a T-helper (Th)1/Th17-mediated chronic inflammatory disease. There is an increased population of Th cells in skin lesions and peripheral circulation of patients with psoriasis. Systemic methotrexate (MTX) is an effective treatment for moderate to severe psoriasis; however, its effect on different T-cell subsets is not yet clear. Aim. To study the effect of MTX monotherapy on the psoriatic T-cell profile in the peripheral circulation of patients with psoriasis.Methods. This was a follow-up study involving 50 patients with moderate to severe psoriasis treated with systemic MTX for 12 weeks. Blood samples (5 mL) were collected from participants, from which PBMCs were isolated, and T-cell phenotyping was performed by flow cytometry. Results. Following 12 weeks of MTX treatment, there was an increase in the percentages of Th2/Treg cells, and a relative decrease in the percentages of Th1/Th17 cells, along with a significant reduction in the median Psoriasis Area and Severity Index (PASI). Conclusion. MTX helps in the restoration of the immune balance by decreasing the numbers of Th1 and Th17 cells and increasing the numbers of Th2 and Treg cells, thus resulting in a significant reduction in disease severity. MTX converts a proinflammatory T-cell phenotype to a protective anti-inflammatory phenotype, thus significantly suppressing the inflammation in psoriasis.

Activated, Pro-Inflammatory Th1, Th17, and Memory CD4+ T Cells and B Cells Are Involved in Delayed-Type Hypersensitivity Arthritis (DTHA) Inflammation and Paw Swelling in Mice

“…MTX reduced the proportion of activated CD4+ T cells in both DTHA mice and in vitro (Supplementary Figure 6). Additionally, MTX diminished DTHA-induced increased level of Th1 cells, which is consistent with previous studies showing that MTX can effectively suppress both Th1 cell population and its cytokine production, such as IFN-g (73)(74)(75). This was in contrast to DEX, which failed to affect any of CD4+ T cell subsets proportion in iLN.…”

A randomised clinical trial of methotrexate points to possible efficacy and adaptive immune dysfunction in psychosis

“…Methotrexate is known to increase tissue levels of adenosine, a potent anti-inflammatory molecule, and this is also mediated by Tregs 14 . These actions restore an anti-inflammatory cytokine profile in autoimmune diseases 3,17 . Given the well-known comorbidity and shared familial risk between schizophrenia and autoimmune disorders 18,19 , the possible antipsychotic efficacy of methotrexate is of considerable aetiological significance for schizophrenia.…”

Role of regulatory T cells in psoriasis pathogenesis and treatment

“…89,90 In the treatment of psoriasis, methotrexate decreases the frequency of Th1 and Th17 cells while simultaneously promoting the accumulation of Th2 cells and Tregs. 115 Further, decreased suppressive function of IL-17-secreting Tregs resulting from reduced CD73 expression could be recovered by methotrexate treatment. 91 Vitamin D treatment induces a cytokine profile favouring the differentiation of T cells with suppressive phenotypes.…”

“…The folic acid analogue methotrexate acts not only through folate antagonism but also mediates anti‐inflammatory effects via adenosine, 114 which enhances Treg numbers and function 89,90 . In the treatment of psoriasis, methotrexate decreases the frequency of Th1 and Th17 cells while simultaneously promoting the accumulation of Th2 cells and Tregs 115 . Further, decreased suppressive function of IL‐17‐secreting Tregs resulting from reduced CD73 expression could be recovered by methotrexate treatment 91 …”