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

• Published in: Experimental dermatology 2022-02, Vol.31 (2), p.191-201
• Main Authors: Virgens, Anangélica R., Goes, Heliana F. O., Carvalho, Gabriel C., Pietrobon, Anna Julia, C. C. Branco, Anna Cláudia, Ramos, Yasmim A. L., Pereira, Naiura V., Orfali, Raquel L., Aoki, Valéria, Silva, Luiz Fernando F., Sotto, Mirian N., Reis, Vitor M.S., Sato, Maria N.
• Format: Article
• Language: English
• Subjects: allergic contact dermatitis; Atopic dermatitis; Biopsy; CD163 antigen; CD4 antigen; Contact dermatitis; Dermatitis; Dermatitis, Allergic Contact; Gene expression; Helper cells; Humans; Immunofluorescence; Immunohistochemistry; Immunopathogenesis; Interleukin-13; Interleukin-4; Lymphocytes; Lymphocytes T; Macrophages; methylchloroisothiazolinone; methylisothiazolinone; Patch Tests - adverse effects; Patch Tests - methods; RNA, Messenger; Skin tests; Stat1 protein; Th2 Cells; Thiazoles; Transcription
• ISSN: 0906-6705; 1600-0625
• DOI: 10.1111/exd.14442

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. 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.