Perivascular clusters of Th2 cells and M2 macrophages in allergic contact dermatitis to methylchloroisothiazolinone and methylisothiazolinone. Issue 2 (11th August 2021)

• Record Type: Journal Article
• Authors: Virgens, Anangélica R.; Goes, Heliana F. O.; de Carvalho, Gabriel C.; Pietrobon, Anna Julia; C. C. Branco, Anna Cláudia; Ramos, Yasmim A. L.; Pereira, Naiura V.; Orfali, Raquel L.; Aoki, Valéria; da Silva, Luiz Fernando F.; Sotto, Mirian N.; dos Reis, Vitor M.S.; Sato, Maria N.
• Is Part Of: Experimental dermatology. Volume 31:Issue 2(2022)
• Page Start: 191
• Page End: 201
• Publication Date: 2021-08-11
• Subjects: allergic contact dermatitis -- macrophages -- methylchloroisothiazolinone -- methylisothiazolinone -- Th2 cells; Dermatology -- Periodicals; 616.5
• DOI: 10.1111/exd.14442
• Languages: English
• ISSNs: 0906-6705

Abstract

Abstract: Background: Methylisothiazolinone (MI) and Methylchloroisothiazolinone (MCI) are among the most common skin sensitizers, yet the immunological events that occur during MCI/MI allergic contact dermatitis (ACD) are still poorly understood. Objectives: To analyse dendrocytes, macrophage subtypes and T cells in skin during the elicitation phase of MCI/MI ACD. Methods: Thirteen patients with positive patch test reactions to MCI/MI (ACD group) and 11 individuals with negative patch test results were selected. Skin biopsies were only performed at 48 hours of patch testing. Immunohistochemistry was conducted to assess T cells, dendrocytes (Factor XIIIa), M1 (p‐Stat1, CD68) and M2 (c‐Maf, CD163) macrophages. Transcriptional analyses were performed for cytokines and related factors, and further compared to atopic dermatitis samples (n=4). Immunofluorescence assays addressed T cells location, along with IL‐4 or IL‐13, within the skin. Results: MCI/MI elicited dermal dendrocytes and macrophages, pronouncedly the M2 subtype. T cells, majorly CD4+ T cells, accumulated in the perivascular areas. Similarly, abundant IL‐4 protein was detected in these areas. There was an upregulation of IL‐4 and IL‐13 mRNA expression, a mild increase in IFNG mRNA levels and a down‐regulation of RORC in the ACD group. Immunofluorescence revealed dermal clusters of T cells co‐localized with IL‐4. Conclusions: M2 macrophages and Th2 cells participate in the immunopathogenesis of MCI/MI ACD. Dermal dendrocytes and M2 macrophages may assist the formation of CD4+ T cells perivascular clusters. These findings render a mechanistic insight into the MCI/MI reaction. Further analysis at different timepoints of patch testing is required to fully comprehend this ACD kinetics. Abstract : Perivascular clusters of IL‐4–secreting T cells are formed during the elicitation phase of ACD to MCI/MI. Dermal M2 macrophages and perivascular Th2 cells participate in the immunopathogenesis of ACD to MCI/MI. These findings bring forward the possibility of new therapeutic approaches to ACD to MCI/MI, through inhibiting the cells, receptors or cytokines involved in the reaction.