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J. Allergy Clin. Immunol., February 18, 2025 | DOI: 10.1016/j.jaci.2025.02.008
Psoriasis Harbors Multiple Pathogenic Type 17 T-cell Subsets: Selective Modulation by Risankizumab
Jaehwan Kim, MD, PhDa,b,c∙ Jongmi Lee, MD, PhDa,b ∙ Jongeun Lee, MDc ∙ Katherine Kima,b ∙ Xuan Li, BSc ∙ Wei Zhou, PhDd ∙ Junyue Cao, PhDd ∙ James G. Krueger, MD, PhDc
aDepartment of Dermatology, University of California, Davis, Sacramento, California, USA
bDermatology Section, Veterans Affairs Northern California Health Care System, Mather, California, USA
cLaboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA
dLaboratory of Single-cell Genomics and Population Dynamics, The Rockefeller University, New York, New York, USA
Correspondence : Jaehwan Kim, MD, PhD, James G. Krueger, MD, PhD
aDepartment of Dermatology, University of California, Davis, Sacramento, California, USA
bDermatology Section, Veterans Affairs Northern California Health Care System, Mather, California, USA
cLaboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA
dLaboratory of Single-cell Genomics and Population Dynamics, The Rockefeller University, New York, New York, USA
Correspondence : Jaehwan Kim, MD, PhD, James G. Krueger, MD, PhD
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 of them in human psoriasis skin. However, it is unknown how T17 subsets are differently regulated by IL-23 versus IL-17A blockades.
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 non-lesional skin, 12 psoriasis posttreatment after IL-23 inhibition, 4 psoriasis posttreatment after IL-17A inhibition, and 10 control skin samples.
Results
Of the six T17 cell 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 non-pathogenic 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.
Recent single-cell studies indicated that IL-17-producing T-cells (T17) have diverse subsets expressing IL-17A, IL-17F, or a combination of them in human psoriasis skin. However, it is unknown how T17 subsets are differently regulated by IL-23 versus IL-17A blockades.
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 non-lesional skin, 12 psoriasis posttreatment after IL-23 inhibition, 4 psoriasis posttreatment after IL-17A inhibition, and 10 control skin samples.
Results
Of the six T17 cell 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 non-pathogenic 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.
논문정보
- Research article
- 2025년 02월 (BRIC 등록일 2025-02-21)
- 국외 연구진
- 의약학 > 응용의학
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