Psoriasis harbors multiple pathogenic type 17 T-cell subsets: Selective modulation by risankizumab - 04/06/25
, Jongmi Lee, MD, PhD a, b, Jongeun Lee, MD c, Katherine Kim a, b, Xuan Li, BS c, Wei Zhou, PhD d, Junyue Cao, PhD d, James G. Krueger, MD, PhD c, ⁎ Graphical abstract |
Abstract |
Background |
Recent single-cell studies indicated that IL-17–producing T cells (T17) have diverse subsets expressing IL-17A, IL-17F, or a combination in human psoriasis skin. However, it is unknown how T17 subsets are differently regulated by IL-23 versus IL-17A blockade.
Objective |
We sought to investigate how systemic monoclonal antibody injections blocking IL-23 versus IL-17A differently modify immune cell transcriptomes in human psoriasis skin.
Methods |
We analyzed a total of 93 human skin single-cell libraries, including 42 psoriasis pretreatment lesional skin, 25 psoriasis pretreatment nonlesional skin, 12 psoriasis posttreatment after IL-23 inhibition, 4 psoriasis posttreatment after IL-17A inhibition, and 10 control skin samples. ClinicalTrials.gov NCT04630652.
Results |
Of the six T17 subsets identified, an IL17A+IFNG+ subset and an IL17F+IL10− subset expressed the IL-23 receptor along with other inflammatory cytokines, and IL-23 inhibition downregulated these potentially pathogenic T17 subsets. In contrast, T17 cells expressing both IL-17A and IL-17F did not express the IL-23 receptor, and the percentage of this potentially nonpathogenic T17 subset increased after IL-23 inhibition. In addition, the expression of the IL-17–negative regulation genes, such as TNFAIP3, increased in myeloid cells more after IL-23 inhibition than after IL-17A inhibition.
Conclusions |
This study suggests multiple immune mechanisms of how IL-23 inhibition can modify the complex inflammatory environment present in psoriatic skin, highlighting the roles of specific T17 subsets in psoriasis development and background skin protection.
Le texte complet de cet article est disponible en PDF.Key words : Psoriasis, IL-17A, IL-17F, IL-23, type 17 T cells, single-cell RNA sequencing, T cell, dendritic cell, myeloid cell, keratinocyte
Abbreviations used : DC, DC3, FCH, FDR, GEO, IL23R, KC, LS, NL, PASI, scRNA-Seq, T17, TNFAIP3, TRM, TRM17
Plan
Vol 155 - N° 6
P. 1898-1912 - juin 2025 Retour au numéro
Article précédent
- Cigarette smoke–induced epithelial cell ferroptosis promotes neutrophilic inflammation in patients with nasal polyps
- Li Pan, Ze Yu, Wen-Xuan Xiang, Shi-Ran Sun, Jing-Xian Li, Yi-Ke Deng, Meng-Chen Wang, Ji-Xin Zhong, Kun Huang, Pei-Song Gao, Li-Ping Zhu, Yin Yao, Zheng Liu
- IL-36–driven pustulosis: Transcriptomic signatures match between generalized pustular psoriasis (GPP) and acute generalized exanthematous pustulosis (AGEP)
- Theresa Benezeder, Natalie Bordag, Johannes Woltsche, Katharina Falkensteiner, Thomas Graier, Eva Schadelbauer, Lorenzo Cerroni, Damian Meyersburg, Valeria Mateeva, Adam Reich, Marta Kołt-Kamińska, Gudrun Ratzinger, Julia-Tatjana Maul, Barbara Meier-Schiesser, Alexander A. Navarini, Romana Ceovic, Knut Prillinger, Maruska Marovt, Lev Pavlovksy, Andrea Szegedi, Maria Sanzharovskaja, Herwig Zach, Peter Wolf
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?