Shunya Mashiko1, Salim Bouguermouh1, Manuel Rubio1, Nobuyasu Baba2, Robert Bissonnette3, Marika Sarfati4. 1. Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada. 2. Center for Innovative and Translational Medicine, Kochi University Medical School, Nankoku, Kochi, Japan. 3. Innovaderm Research, Montreal, Quebec, Canada. 4. Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada. Electronic address: m.sarfati@umontreal.ca.
Abstract
BACKGROUND: Psoriasis is a systemic inflammatory disease in which IL-17 and IL-22 levels are markedly increased in the skin and blood. The prevalent concept, using skin cells that are isolated from psoriatic plaques and examined after cell expansion and in vitro stimulation, is that IL-17 and IL-22 production essentially results from T cells and the rare type 3 innate lymphoid cells. OBJECTIVE: We sought to examine the cellular source of IL-17A and IL-22 at the protein and transcriptional single-cell level immediately after ex vivo skin cell isolation from psoriatic plaques. METHODS: Skin biopsy specimens were collected from patients with psoriasis, as well as from patients with atopic dermatitis. Cell suspensions were prepared by combining mild enzymatic digestion and mechanical dissociation and analyzed for cytokine expression without prior in vitro culture and stimulation. Expression of IL-17 and IL-22 was quantified at the protein and mRNA single-cell level by using flow cytometry. RESULTS: IL-22 is predominantly expressed by CD3(-)c-Kit(+) cells relative to CD3(+) T cells in lesional skin of patients with psoriasis and patients with atopic dermatitis. Strikingly, we identified c-Kit(+)FcεRI(+) mast cells as major IL-22 producers. The proportion of mast cells that produce IL-22 ranges from 20% to 80% in patients with psoriasis or those with atopic dermatitis. Skin mast cells express IL-22 and IL-17 mRNA. Conversely, IL-17-producing T cells outnumber IL-17-producing mast cells, which also express IL-17 receptor. CONCLUSION: Human skin mast cells are previously unrecognized IL-22 producers. We further established that skin mast cells express IL-17. Thus mast cells might play an important role in the physiopathology of chronic inflammatory skin disorders.
BACKGROUND:Psoriasis is a systemic inflammatory disease in which IL-17 and IL-22 levels are markedly increased in the skin and blood. The prevalent concept, using skin cells that are isolated from psoriatic plaques and examined after cell expansion and in vitro stimulation, is that IL-17 and IL-22 production essentially results from T cells and the rare type 3 innate lymphoid cells. OBJECTIVE: We sought to examine the cellular source of IL-17A and IL-22 at the protein and transcriptional single-cell level immediately after ex vivo skin cell isolation from psoriatic plaques. METHODS: Skin biopsy specimens were collected from patients with psoriasis, as well as from patients with atopic dermatitis. Cell suspensions were prepared by combining mild enzymatic digestion and mechanical dissociation and analyzed for cytokine expression without prior in vitro culture and stimulation. Expression of IL-17 and IL-22 was quantified at the protein and mRNA single-cell level by using flow cytometry. RESULTS:IL-22 is predominantly expressed by CD3(-)c-Kit(+) cells relative to CD3(+) T cells in lesional skin of patients with psoriasis and patients with atopic dermatitis. Strikingly, we identified c-Kit(+)FcεRI(+) mast cells as major IL-22 producers. The proportion of mast cells that produce IL-22 ranges from 20% to 80% in patients with psoriasis or those with atopic dermatitis. Skin mast cells express IL-22 and IL-17 mRNA. Conversely, IL-17-producing T cells outnumber IL-17-producing mast cells, which also express IL-17 receptor. CONCLUSION:Human skin mast cells are previously unrecognized IL-22 producers. We further established that skin mast cells express IL-17. Thus mast cells might play an important role in the physiopathology of chronic inflammatory skin disorders.
Authors: Linghui Xu; Wanhong Ding; Lori L Stohl; Xi K Zhou; Shayan Azizi; Ethan Chuang; Jimmy Lam; John A Wagner; Richard D Granstein Journal: Immunology Date: 2017-12-20 Impact factor: 7.397
Authors: Yan Zhou; Taylor Follansbee; Xuesong Wu; Dan Han; Sebastian Yu; Dan T Domocos; Zhenrui Shi; Mirela Carstens; Earl Carstens; Samuel T Hwang Journal: J Dermatol Sci Date: 2018-11-26 Impact factor: 4.563
Authors: Amina Abdul Qayum; Anuya Paranjape; Daniel Abebayehu; Elizabeth Motunrayo Kolawole; Tamara T Haque; Jamie Josephine Avila McLeod; Andrew J Spence; Heather L Caslin; Marcela T Taruselli; Alena P Chumanevich; Bianca Baker; Carole A Oskeritzian; John J Ryan Journal: J Immunol Date: 2016-04-29 Impact factor: 5.422