Transcriptomes of MPO-Deficient Patients with Generalized Pustular Psoriasis Reveals Expansion of CD4+ Cytotoxic T Cells and an Involvement of the Complement System

Haskamp S, Frey B, Becker I, Schulz-Kuhnt A, Atreya I, Berking C, Pauli D, Ekici AB, Berges J, Mößner R, Wilsmann-Theis D, Sticherling M, Uebe S, Kirchner P, Hüffmeier U (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Journal of Investigative Dermatology Elsevier

DOI: 10.1016/j.jid.2021.12.021

Abstract

Generalized pustular psoriasis is a severe psoriatic subtype characterized by epidermal neutrophil infiltration. Although variants in IL36RN and MPO have been shown to affect immune cells, a systematic analysis of neutrophils and PBMC subsets and their differential gene expression dependent on MPO genotypes was not performed yet. We assessed the transcriptomes of MPO-deficient patients using single-cell RNA sequencing of PBMCs and RNA sequencing of neutrophils in a stable disease state. Cell-type annotation by multimodal reference mapping of single-cell RNA-sequencing data was verified by flow cytometry of surface and intracellular markers; the proportions of CD4+ cytotoxic T lymphocytes and other CD4+ effector cells were increased in generalized pustular psoriasis, whereas the frequencies of naïve CD4+ T cells were significantly lower. The expression of FGFBP2 marking CD4+ cytotoxic T lymphocytes and CD8+ effector memory T cells was elevated in patients with generalized pustular psoriasis with disease-contributing variants compared with that in noncarriers (P = 0.0015). In neutrophils, differentially expressed genes were significantly enriched in genes of the classical complement activation pathway. Future studies assessing affected cell types and pathways will show their contribution to generalized pustular psoriasis's pathogenesis and indicate whether findings can be transferred to the acute epidermal situation and whether depletion or inactivation of CD4+ cytotoxic T lymphocytes may be a reasonable therapeutic approach.

Authors with CRIS profile

Stefan Haskamp Lehrstuhl für Humangenetik Benjamin Frey Department of Radiation Oncology Ina Becker Department of Radiation Oncology Anja Schulz-Kuhnt Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Imke Atreya Medizinische Fakultät Carola Berking Lehrstuhl für Haut- und Geschlechtskrankheiten Arif Bülent Ekici Lehrstuhl für Humangenetik Johannes Berges Department of Medicine 5 – Haematology and Oncology Michael Sticherling Professur für Dermatologie Steffen Uebe Institute of Human Genetics Ulrike Hüffmeier Medizinische Fakultät

Involved external institutions

Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) Georg-August-Universität Göttingen DE Germany (DE)

How to cite

APA:

Haskamp, S., Frey, B., Becker, I., Schulz-Kuhnt, A., Atreya, I., Berking, C.,... Hüffmeier, U. (2022). Transcriptomes of MPO-Deficient Patients with Generalized Pustular Psoriasis Reveals Expansion of CD4+ Cytotoxic T Cells and an Involvement of the Complement System. Journal of Investigative Dermatology. https://doi.org/10.1016/j.jid.2021.12.021

MLA:

Haskamp, Stefan, et al. "Transcriptomes of MPO-Deficient Patients with Generalized Pustular Psoriasis Reveals Expansion of CD4+ Cytotoxic T Cells and an Involvement of the Complement System." Journal of Investigative Dermatology (2022).

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