Regulation of immune response genes in the skin of allergic and clinically tolerant individuals exposed to p‐phenylenediamine

Background p‐Phenylenediamine (PPD) is a potent contact allergen found in many hair colour products. However, not all individuals develop allergic contact dermatitis (ACD) although they are regularly exposed to PPD. It is unclear whether these asymptomatic individuals are true non‐responders to PPD or whether they mount a response to PPD without showing any symptoms. Methods Skin biopsies were collected from 11 asymptomatic hairdressers regularly exposed to PPD and from 10 individuals with known ACD on day 4 after patch testing with 1% PPD in petrolatum and petrolatum exclusively as control. RNA sequencing and confocal microscopy were performed. Results T cell activation, inflammation and apoptosis pathways were up‐regulated by PPD in both asymptomatic and allergic individuals. Compared to asymptomatic individuals with a negative patch test, individuals with a strong reaction to PPD strongly up‐regulated both pro‐ and anti‐inflammatory cytokines genes. Interestingly, PPD treatment induced significant up‐regulation of several genes for chemokines, classical type 2 dendritic cell markers and regulatory T cell markers in both asymptomatic and allergic individuals. In addition, apoptosis signalling pathway was activated in both non‐responders and allergic individuals. Conclusion This study demonstrates that there are no true non‐responders to PPD but that the immune response elicited by PPD differs between individuals and can lead to either tolerance, subclinical inflammation or allergy. T cell activation, inflammation and apoptosis pathways were up‐regulated by PPD in both asymptomatic and allergic individuals. Individuals with a strong reaction to PPD strongly up‐regulated both pro‐ and anti‐inflammatory cytokines genes compared to asymptomatic individuals. The balance between inflammatory and anti‐inflammatory mechanisms that determines whether a given individual develops allergy or tolerance to PPD.Abbreviations: CASP, caspase; CCL, C‐C motif chemokine ligand; CTLA‐4, cytotoxic T‐lymphocyte associated protein 4; CXCL, C‐X‐C motif chemokine ligand; FADD, FAS‐associated death domain protein; FAS, Fas Cell Surface Death Receptor; FASLG, Fas ligand; FOXP3, forkhead box P3; GATA3, GATA binding protein 3; GZMB, granzyme B; IFNG, interferon gamma; IL, interleukin; LTA, lymphotoxin Alpha; PPD, p‐Phenylenediamine; PTPRC, Protein Tyrosine Phosphatase Receptor Type C; RNA‐seq, RORC, RAR related orphan receptor C; RNA sequencing; TBX21, T‐box transcription factor; TNF