*4.1. Cell Culture*

This study was conducted in agreemen<sup>t</sup> with the Helsinki Declaration and performed under the guidelines of the Research Ethics Committee of the Centre de recherche du CHU de Québec – Université Laval. All patients were given adequate information for providing written consent. Two di fferent patients with psoriasis aged 46 and 49 years old, respectively, were recruited. Six-millimeter punch biopsies were taken from psoriatic skin. As for the healthy skin substitutes, biopsies were obtained from healthy donors during breast reduction surgeries. Healthy donors were Caucasian females aged 46 and 49 years old. Cells were extracted according to the method based on thermolysin, trypsin, and collagenase digestions described elsewhere [53].

## *4.2. Skin Substitute Production*

All skin substitutes were produced according to the self-assembly method of tissue engineering [13]. Briefly, fibroblasts at passage 6 were seeded in 6-well plates at 0.12 × 10<sup>6</sup> cells per well. Fibroblasts were cultured in Dulbecco's modified Eagle's medium (DME) (Gibco, Life Technologies, New York, NY, USA) supplemented with 10% Fetal Calf premium Serum (FCS) (Wiscent, Inc., St-Bruno, QC, Canada), 50 μg/mL ascorbate acid (Sigma, Oakville, ON, Canada) and antibiotics; 60 μg/mL penicillin G (Sigma, Oakville, ON, Canada) and 25 μg/mL gentamicin (Schering, Pointe-Claire, QC, Canada). After 28 days, dermal cells formed sheets that were superimposed and cultured for another 2 d. After that, keratinocytes at passage 2 were seeded at 1.2 × 10<sup>6</sup> cells upon each tissue sheet to form the epidermal layer. Another 7 days of culture allowed the epidermal cells to grow, and then each substitute was raised to the air-liquid interface and cultured for a total of 21 days. Keratinocytes were cultured in DME mixed with Ham's F12 medium (3:1) (DME-HAM) (Gibco, Life Technologies, New York, NY, USA) supplemented with 5% FetalClone II serum (Hyclone, Logan, UT, US), 5 μg/mL insulin (Sigma, Oakville, ON, Canada), 0.4 μg/mL hydrocortisone (Galenova, St-Hyacinthe, QC, Canada), 10 ng/mL human epidermal growth factor (EGF) (Ango Inc, San Ramon, CA, USA), 60 μg/mL penicillin, and 25 μg/mL gentamicin. Keratinocyte culture media were also supplemented with either 10−<sup>10</sup> M cholera toxin (MP Biomedicals, Montreal, QC, Canada) or 10−<sup>6</sup> M isoproterenol (rISO; Sigma Aldrich, St. Louis, MO, USA).
