Perivascular clusters of Th2 cells and M2 macrophages in allergic contact dermatitis to methylchloroisothiazolinone and methylisothiazolinone

• DOI: 10.1111/exd.14442
• Publication Date: 2021-08-06T19:01:11Z
• Authors: Anangélica R. Vir...; Heliana F. O. Goes; Gabriel C. de Car...; Anna Julia Pietrobon; Anna Cláudia C. C...; Yasmim A. L. Ramos; Naiura V. Pereira; Raquel L. Orfali; Valéria Aoki; Luiz Fernando F. ...; Mirian N. Sotto; Vitor M.S. dos Reis; Maria N. Sato
• Keywords: 0301 basic medicine; Thiazoles; 03 medical and health sciences; Interleukin-13; Th2 Cells; Macrophages; Dermatitis, Allergic Contact; Humans; Interleukin-4; RNA, Messenger; Patch Tests; 3. Good health

AbstractBackgroundMethylisothiazolinone (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.MethodsThirteen 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.ResultsMCI/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.ConclusionsM2 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.