In the skin lesions of patients with mycosis fungoides, the number of MRGPRX2-expressing cells is increased and correlates with mast cell numbers.

Background

Mycosis fungoides (MF) is an indolent T-cell lymphoma that mainly affects the skin and presents with itch in more than half of the patients. Recently, the expression of Mas-related G protein-coupled receptor X2 (MRGPRX2), a receptor of mast cell (MC) responsible for the IgE-independent non-histaminergic itch, has been shown in lesional skin of patients with pruritic skin diseases, including chronic urticaria, prurigo, and mastocytosis. As of yet, limited knowledge exists regarding the MRGPRX2 expression in the skin of patients with MF.

Objectives

To investigate the number of MRGPRX2-expressing (MRGPRX2+) cells in the skin of patients with MF and its correlation with clinical and laboratory characteristics of the disease.

Methods

MRGPRX2 was analyzed in lesional and non-lesional skin of MF patients and healthy skin tissues by immunohistochemistry. Co-localization of MRGPRX2 with the MC marker tryptase was assessed by immunofluorescence. Public single-cell RNAseq data was reanalyzed to identify the MRGPRX2 expression on the distinct cell types.

Results

In lesional skin of MF patients, MRGPRX2+ cell number was higher than in non-lesional skin and healthy control skin (mean:15.12 vs. 6.84 vs. 5.51 cells/mm

Conclusions

Our findings point to the role of MRGPRX2 and MC in the pathogenesis of MF that should be investigated in further studies.

Informations de copyright

Copyright © 2023 Hu, Pyatilova, Altrichter, Sheng, Liu, Terhorst-Molawi, Lohse, Ginter, Puhl, Maurer, Metz and Kolkhir.

Déclaration de conflit d'intérêts

SA has conducted studies for/was advisor for/was speaker for AstraZeneca, Allakos, ALK, Biocryst, CSLBehring, LeoPharma, Moxie, Novartis, Pharvaris, Sanofi, Takeda, Thermofisher. MaMe received honoraria advisory board, speaker from AbbVie, Amgen, AstraZeneca, argenx, Bayer, Beiersdorf, Celldex, Escient, Galderma, gsk, Jasper, Novartis, Pharvaris, Pfizer, Sanofi-Aventis, Tevapharm, ThirdHarmonicBio, Viforpharma, outside of submitted work. PK received honoraria advisory board, speaker from Novartis, Roche and ValenzaBio, outside of submitted work. Outside of this work, MMa is or recently was a speaker and/or advisor for and/or has received research funding from Astria, Allakos, Alnylam, Amgen, Aralez, ArgenX, AstraZeneca, BioCryst, Blueprint, Celldex, Centogene, CSL Behring, Dyax, FAES, Genentech, GIInnovation, GSK, Innate Pharma, Kalvista, Kyowa Kirin, Leo Pharma, Lilly, Menarini, Moxie, Novartis, Pfizer, Pharming, Pharvaris, Roche, Sanofi/Regeneron, Shire/Takeda, Third Harmonic Bio, UCB, and Uriach. DT-M has received research funds and/or was advisor for Celldex, Moxie, Novartis and Sanofi. Outside of this work, CS is an employee of the GV20 Therapeutics, which develops drugs and research models for profit. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.