Evidence for a restoration of TLR2 response in epidermal dendritic cells in atopic dermatitis by topical anti‐inflammatory therapy

• DOI: 10.1111/all.15899
• Publication Date: 2023-09-25T08:54:51Z
• Authors: Marie‐Sophie Philipp; Tim J. Nümm; Yuxuan Deng; Kazumasa Iwamoto; Nadine Herrmann; Thomas Bieber
• Keywords: Langerhans Cells; Administration, Topical; Anti-Inflammatory Agents; Humans; Dendritic Cells; Toll-Like Receptor 2; Dermatitis, Atopic; Skin

Patients suffering from atopic dermatitis (AD) show an attenuated immune response and imbalanced microbiome environment that favors Staphylococcus aureus (S. aureus).1 Bacterial products are recognized via Toll-like receptors (TLR) of the system leading to maturation dendritic cells (DC).2 Recently, we showed Langerhans (LC), DC in epidermis, ex vivo AD skin had inhibited toward TLR2 stimulation when compared healthy controls (HC).3 Topical anti-inflammatory treatment reduces inflammation colonization with S. aureus.4 To test its impact on expression function epidermal DC, analyzed freshly isolated lesional treated (topical steroids or tacrolimus for 2 days [median]) untreated patients as well HC (for methods see Appendix S1). LC elevated similar CD83 MHCII AD, confirming our previous results (Figure 1). was lower AD. CD80 significantly higher described,5 but independent treatment. maturation-associated marker 1) inflammatory (IDEC) S1) failed significant differences upon except LC. Upon treatment, only levels were decreased. However, it has been reported 1 week is able reduce markers like CD86 LC.6 The short duration study may explain expression. We further explored ability respond TLR stimulus. Therefore, cultured shave biopsy presence absence TLR2-specific ligand Pam3Cys mimicking aureus-derived signals. a clear downregulation upregulation CD83, while lack described previously3 2). A trend observed limited number experiments, though this be considered preliminary. under these conditions.3 Taken together conclude restores ligands measurable molecular level shortly after before macroscopic clearance skin. confirmed by separated analysis less than 4 days. S2). Additionally, IDEC (Figures S3,S4), suggesting general mechanism responsiveness restoration In contrast tolerance skin, topical seems abrogate again capable responding stimulation. One explanation fitting overall picture activated situ due local microenvironment including impaired barrier, inflammation, constant exposure aureus, functional capacity DC. addition, disinfected still harbors dead particles influence activation during cell culture. one would expect also case there no sign control conditions. skin's load not here. Another limit exclusion migrated analyses. Besides surface cytokine production. production IL-6 IL-10 enhanced By contrast, IL-18 reduced S5). These measured controls3 indicating adjusted more status mechanisms remain elucidated. summary, changes briefly CD83. Nevertheless, restore reactivity, where increased receptor Though remains speculative if restauration TLR2-signaling initial starting point improvement, strongly suggest signaling lesion rapidly phenotypical detected. Marie-Sophie Philipp performing data analyses interpretation, statistical analyses, writing manuscript. Tim Nümm manuscript draft. Kazumasa Iwamoto experiments Yuxuan Deng critical reviewing manuscript, experiments. Nadine Herrmann supervision, conceptional input, revision Thomas Bieber design, recruitment, thank all their donation, Dr. Lisa Braun, Sophie Kläschen, Laura Maintz Department Dermatology Allergy, University Bonn, Germany, Helene Kirins Sylvia Schnautz expert technical assistance. K. Walgenbach Plastic Aesthetic Surgery, providing us normal samples. Open Access funding enabled organized Projekt DEAL. This supported Christine Kühne—Center Allergy Research Education (CK-CARE). J. Nümm, Philipp, Deng, CK-CARE. Bieberer speaker, and/or consultant, investigator for: AbbVie, Allmiral, AnaptysBio, Arena, Asana Biosciences, Astellas, BioVerSys, Böhringer Ingelheim, Celgene, Daiichi Sankyo, Dermavant/Roivant, DermTreat, DS Pharma, RAPT/ FLX Bio, Galapagos/MorphoSys, Galderma, Glenmark, GSK, Incytes, Kymab, LEO, Lilly, L'Oréal, MenloTx, Novartis, Pfizer, Pierre Fabre, Sanofi/Regeneron, UCB. founder nonprofit biotech company “Davos Biosciences”. All other authors have conflicts interest declare. shared. Figure S1 S2 S3 S4 S5 Please note: publisher responsible content functionality any supporting information supplied authors. Any queries (other missing content) should directed corresponding author article.