TY - JOUR
T1 - Delayed type hypersensitivity reactions to various allergens may differently model inflammatory skin diseases
AU - Pavel, Ana B.
AU - Del Duca, Ester
AU - Cheng, Julia
AU - Wu, Jianni
AU - Ungar, Benjamin
AU - Estrada, Yeriel D.
AU - Jack, Carolyn
AU - Maari, Catherine
AU - Proulx, Étienne Saint Cyr
AU - Ramirez-Valle, Francisco
AU - Krueger, James G.
AU - Bissonnette, Robert
AU - Guttman-Yassky, Emma
N1 - Funding Information:
This research was supported by a grant from Celgene Inc.
Funding Information:
EGY is an employee of Mount Sinai and has received research funds (grants paid to the institution) from: Abbvie, Celgene, Eli Lilly, Janssen, Medimmune/Astra Zeneca, Novartis, Pfizer, Regeneron, Vitae, Glenmark, Galderma, Asana, Innovaderm, Dermira, UCB. EGY is also a consultant for Sanofi Aventis, Regeneron, Stiefel/GlaxoSmithKline, MedImmune, Celgene, Anacor, AnaptysBio, Dermira, Galderma, Glenmark, Novartis, Pfizer, Vitae, Leo Pharma, Abbvie, Eli Lilly, Kyowa, Mitsubishi Tanabe, Asana Biosciences, and Promius. RB is an Investigator, Consultant, Advisory Board Member, Speaker for and/or receives honoraria or grant from AbbVie, Amgen, AntibioTx, Aquinox Pharma, Arcutis, Asana BioSciences, Astellas, Bausch Health Immune Pharma, Bausch Health Immune Pharma, Boehringer Ingelheim, Brickell Biotech, Bristol‐Myers Squibb, Celgene, Dermavant, Dermira, Dignity Sciences, Eli Lilly, Escalier, Galderma, Glenmark, GSK‐Stiefel, Hoffman LaRoche Posay, Immune Tolerance, Janssen, Kineta, Kiniksa, Leo Pharma, Merck, Neokera, Pfizer, Regeneron, Sanofi, Sienna, UCB, Valeant, Vitae, and Xenoport. RB is also an employee and shareholder of Innovaderm Research. JGK has received research support (grants paid to his institution) and/or personal fees from Pfizer, Amgen, Janssen, Lilly, Merck, Novartis, Kadmon, Dermira, Boehringer, Innovaderm, Kyowa, BMS, Serono, BiogenIdec, Delenex, AbbVie, Sanofi, Baxter, Paraxel, Xenoport, and Kineta. ABP is an employee of the Icahn School of Medicine at Mount Sinai and performs research sponsored by Pfizer and Regeneron. BU is an employee of Mount Sinai and has received research funds (grants paid to the institution) from: Incyte, Rapt Therapeutics, Pfizer, and he is a consultant for Arcutis Biotherapeutics and Castle Biosciences. CJ reports grants from Innovaderm Research, McGill University Department of Medicine, MITACS, Canadian Dermatology Foundation, and Eczema Society of Canada, as well as grants, involvement in clinical studies, and/or consultancy work for Sanofi, Eli Lilly, AbbVie, Novartis, Valeant, Bausch, Pfizer, Amgen, Celgene, Janssen, Boehringer Ingelheim, Asana, LEO, Dermavant, AntibioTx, Neokera, Kiniksa, Ralexar, Arcutis, BMS, Boston, Cara, Concert, Incyte, Sienna, Aristea, Target PharmaSolution, and UCB. ESCP is an Investigator, Consultant, Advisory Board Member, Speaker for and/or receives honoraria or grant from AbbVie, AntibioTx, Arcutis, Aristea, Bausch Health/Valeant, Boehringer Ingelheim, Concert Pharmaceuticals, Dermavant Sciences, Eli Lilly, Escalier, Janssen Pharmaceuticals, LEO Pharma, Pfizer, Regeneron Pharmaceuticals Inc., Sanofi, Sienna Biopharmaceuticals Inc., and UCB. FRV is an employee and shareholder of Bristol Myers Squibb. The remaining authors have no conflicts of interest to disclose.
Publisher Copyright:
© 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
PY - 2023/1
Y1 - 2023/1
N2 - Background: Treatment of inflammatory skin diseases, including atopic dermatitis (AD) and psoriasis, is undergoing transformative changes, highlighting the need to develop experimental models of skin inflammation in humans to predict treatment responses. Methods: We topically or intradermally administered four common sensitizers (dust mite (DM), diphencyprone (DPCP), nickel (Ni), and purified protein derivative (PPD)) to the backs of 40 healthy patients and the skin hypersensitivity response was biopsied and evaluated using immunohistochemistry, RNA-seq, and RT-PCR. Results: All agents induced strong increases in cellular infiltrates (T-cells and dendritic cells) as compared to untreated skin (p <.05), with variable T helper polarization. Overall, DPCP induced the strongest immune responses across all pathways, including innate immunity (IL-1α, IL-8), Th1 (IFNγ, CXCL10), Th2 (IL-5, CCL11), and Th17 (CAMP/LL37) products, as well as the highest regulatory tone (FOXP3, IL-34, IL-37) (FDR <0.01). Nickel induced Th17 (IL-17A), Th1 (CXCL10) and Th2 (IL-4R) immune responses to a lesser extent than DPCP (p <.05). PPD induced predominantly Th1 (IFNγ, CXCL10, STAT1) and Th17 inflammation (IL-17A) (p <.05). DM induced modulation of Th2 (IL-13, CCL17, CCL18), Th22 (IL-22), and Th17/Th22 (S100A7/9/12) pathways (p <.05). Barrier defects that characterize both AD and psoriasis were best modeled by DPCP and Ni, followed by PPD, including downregulation of terminal differentiation (FLG, FLG2, LOR, LCEs), tight junction (CLDN1/CLDN8), and lipid metabolism (FA2H, FABP7)-related markers. Conclusion: Our data imply that DPCP induced the strongest immune response across all pathways, and barrier defects characteristic of AD and psoriasis.
AB - Background: Treatment of inflammatory skin diseases, including atopic dermatitis (AD) and psoriasis, is undergoing transformative changes, highlighting the need to develop experimental models of skin inflammation in humans to predict treatment responses. Methods: We topically or intradermally administered four common sensitizers (dust mite (DM), diphencyprone (DPCP), nickel (Ni), and purified protein derivative (PPD)) to the backs of 40 healthy patients and the skin hypersensitivity response was biopsied and evaluated using immunohistochemistry, RNA-seq, and RT-PCR. Results: All agents induced strong increases in cellular infiltrates (T-cells and dendritic cells) as compared to untreated skin (p <.05), with variable T helper polarization. Overall, DPCP induced the strongest immune responses across all pathways, including innate immunity (IL-1α, IL-8), Th1 (IFNγ, CXCL10), Th2 (IL-5, CCL11), and Th17 (CAMP/LL37) products, as well as the highest regulatory tone (FOXP3, IL-34, IL-37) (FDR <0.01). Nickel induced Th17 (IL-17A), Th1 (CXCL10) and Th2 (IL-4R) immune responses to a lesser extent than DPCP (p <.05). PPD induced predominantly Th1 (IFNγ, CXCL10, STAT1) and Th17 inflammation (IL-17A) (p <.05). DM induced modulation of Th2 (IL-13, CCL17, CCL18), Th22 (IL-22), and Th17/Th22 (S100A7/9/12) pathways (p <.05). Barrier defects that characterize both AD and psoriasis were best modeled by DPCP and Ni, followed by PPD, including downregulation of terminal differentiation (FLG, FLG2, LOR, LCEs), tight junction (CLDN1/CLDN8), and lipid metabolism (FA2H, FABP7)-related markers. Conclusion: Our data imply that DPCP induced the strongest immune response across all pathways, and barrier defects characteristic of AD and psoriasis.
KW - allergic contact dermatitis
KW - biomarker
KW - contact dermatitis
KW - inflammation
KW - inflammatory skin disease
UR - http://www.scopus.com/inward/record.url?scp=85139426496&partnerID=8YFLogxK
U2 - 10.1111/all.15538
DO - 10.1111/all.15538
M3 - Article
C2 - 36178084
AN - SCOPUS:85139426496
VL - 78
SP - 178
EP - 191
JO - Allergy: European Journal of Allergy and Clinical Immunology
JF - Allergy: European Journal of Allergy and Clinical Immunology
SN - 0105-4538
IS - 1
ER -