Dataset Information

Methotrexate for refractory adult atopic dermatitis leads to alterations in cutaneous IL-31 and IL-31RA expression.

ABSTRACT:

Background

Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD).

Objective

The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks.

Methods

The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral MTX (15 mg/wk for 24 wks) and 10 non-atopic matched controls. The comparison was made of skin biopsies of lesional and non-lesional skin, pre- and post MTX treatment. The authors analyzed mean epidermal thickness and expression of IL-31, IL-31RA, OSMR, TSLP, Ki67, IL-4 mRNA, IL-6, IL-10, TNF-α, IFN-γ, TARC, and CCL-22.

Results

There was a reduction in mean epidermal thickness (p = 0.021), an increase in IL-31RA expression (immunohistochemistry) in the epidermis (p = 0.016) and a decrease in IL-31 gene expression (p = 0.019) on lesional AD skin post-MTX treatment. No significant changes in the cutaneous expression of the other evaluated markers were identified.

Study limitations

Small sample size and limited length of follow-up.

Conclusions

Treatment with MTX in adults with moderate/severe AD reduced epidermal hyperplasia and changed the cutaneous expression of inflammatory cytokines and receptors that are mainly related to pruritus, including IL-31 and IL-31RA.

Trial registration

ClinicalTrials.gov Identifier: NCT03327116.

SUBMITTER: Samorano LP

PROVIDER: S-EPMC10964359 | biostudies-literature | 2024 Jan-Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Methotrexate for refractory adult atopic dermatitis leads to alterations in cutaneous IL-31 and IL-31RA expression.

Samorano Luciana Paula LP Manfrere Kelly Cristina Gomes KCG Pereira Naiura Vieira NV Takaoka Roberto R Valente Neusa Yuriko Sakai NYS Sotto Mirian Nacagami MN Silva Luiz Fernando Ferraz LFF Sato Maria Notomi MN Aoki Valeria V

Anais brasileiros de dermatologia 20230918 1

<h4>Background</h4>Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD).<h4>Objective</h4>The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks.<h4>Methods</h4>The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral ...[more]

PMID: 37730501

Similar Datasets

Project description:Severe pruritus is a characteristic feature of atopic dermatitis (AD) and is closely related to its activity. Recent studies have shown that IL-31 is a key determinant of pruritus in AD. Anti-IL-31 receptor alpha (IL-31RA) antibody treatment has also been reported to improve pruritus clinically, subsequently contributing to the attenuation of AD disease activity. Therefore, IL-31 has been thought to be an important cytokine for regulating pruritus and AD disease activity; however, how IL-31 is involved in the immune response in AD has remained largely unknown. Epidermal Langerhans cells (LCs) and dermal dendritic cells (DCs) derived from bone marrow cells have been reported to play a critical role in AD pathogenesis. LCs and DCs produce Ccl 17 and Ccl 22, which chemoattract Th2 cells, leading to AD development. Therefore, we aimed to clarify how IL-31/IL-31RA interaction affects Ccl 17 and Ccl 22 production. To test this, we analyzed murine bone marrow-derived DCs (BMDCs) stimulated with IL-4, an important cytokine in AD development. We found that IL-31RA expression was upregulated by IL-4 stimulation in a dose-dependent manner in BMDCs. Furthermore, IL-31 upregulates Ccl 17 and Ccl 22 production in the presence of IL-4, whereas IL-31 stimulation alone did not produce Ccl 17 and Ccl 22. These findings suggest that IL-4 mediates IL-31RA expression and IL-31/IL-31RA interaction augments Ccl 17 and Ccl 22 production in BMDCs, which promotes Th2-deviated immune response in AD. Since we previously reported that soybean tar Glyteer, an aryl hydrocarbon receptor (AHR) ligand, impairs IL-4/Stat 6 signaling in BMDCs, we examined whether Glyteer affects IL-31RA expression induced by IL-4 stimulation. Glyteer inhibited upregulation of IL-31RA expression induced by IL-4 stimulation in a dose-dependent manner. Glyteer also inhibited Ccl 17 and Ccl 22 production induced by IL-4 and IL-31 stimulation. Taken together, these findings suggest that Glyteer treatment may improve AD disease activity by impairing IL-31/IL-31RA interaction in DCs.

Dataset Information

Methotrexate for refractory adult atopic dermatitis leads to alterations in cutaneous IL-31 and IL-31RA expression.

Background

Objective

Methods

Results

Study limitations

Conclusions

Trial registration

Publications

Methotrexate for refractory adult atopic dermatitis leads to alterations in cutaneous IL-31 and IL-31RA expression.

Similar Datasets

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