IL-33 Contributes to the Pathological Changes of Hair Follicles in Psoriasis: A Potential Target for Psoriatic Alopecia
Open Access
- 1 March 2023
- journal article
- research article
- Published by Taylor & Francis Ltd in Clinical, Cosmetic and Investigational Dermatology
- Vol. ume 16, 639-650
- https://doi.org/10.2147/ccid.s403075
Abstract
Purpose: IL-33 is constitutively expressed in skin tissues. Alopecia, a T cells-driven disorder of the hair follicles (HFs), is a common complication in the development of psoriasis. However, the role of IL-33 in psoriatic alopecia remains uncovered. Here, we investigated the roles of IL-33 in inducing pathological changes of hair follicles in psoriasis. Patients and Methods: Clinical samples and imiquimod (IMQ)-induced psoriatic mice samples were used to investigate the pathological changes and T-cell infiltration of HFs. By using immunohistochemistry staining, the distribution and expression alteration of IL-33 in HFs were determined. Next, by using IL-33 and ST2 knockout mice, we investigated the role of IL-33/ST2 axis in the pathological changes of HFs in psoriasis. Meanwhile, recombinant IL-33 protein was subcutaneous injected to confirm its effect. Finally, RNA sequencing was used to clarify the genes and signaling pathways that involved in this process. Differentially expressed genes were further verified by RT-PCR in cultured HFs in vitro. Results: We found that the pathological changes of HFs and T cells infiltration in imiquimod-induced psoriatic mice were similar to that in psoriasis patients. The IL-33 positive keratinocytes in the outer root sheath of HFs were increased in both psoriasis patients and psoriatic model mice compared with the controls. By using gene knockout mice, we found that the pathological changes and T cell infiltration were attenuated in IL-33−/− and ST2−/− psoriatic model mice. In addition, subcutaneous injection of recombinant IL-33 exacerbated the pathological changes of HFs and T cell infiltration. RNA sequencing and RT-RCR revealed that IL-33 upregulated the transcription of genes related to keratinocytes proliferation and T lymphocytes chemotaxis. Conclusion: Our study identifies that IL-33 promotes the pathological changes of HFs in psoriasis, which contributes to psoriatic alopecia. Inhibition of IL-33 may be a potential therapeutic approach for psoriatic alopecia.Keywords
This publication has 51 references indexed in Scilit:
- Epidermal Development in Mammals: Key Regulators, Signals from Beneath, and Stem CellsInternational Journal of Molecular Sciences, 2013
- Contradictory Functions (Activation/Termination) of Neutrophil Proteinase 3 Enzyme (PR3) in Interleukin-33 Biological ActivityOnline Journal of Public Health Informatics, 2012
- Molecular mimicry between IL‐33 and KSHV for attachment to chromatin through the H2A–H2B acidic pocketEMBO Reports, 2008
- A Guide to Assessing Damage Response Pathways of the Hair Follicle: Lessons From Cyclophosphamide-Induced Alopecia in MiceJournal of Investigative Dermatology, 2005
- Interferon-gamma is a potent inducer of catagen-like changes in cultured human anagen hair folliclesBritish Journal of Dermatology, 2005
- Patterns of Proliferation and Apoptosis during Murine Hair Follicle MorphogenesisJournal of Investigative Dermatology, 2001
- Control of hair growth and follicle size by VEGF-mediated angiogenesisJCI Insight, 2001
- Active Hair Growth (Anagen) is Associated with AngiogenesisJournal of Investigative Dermatology, 2000
- Effects of interleukins, colony-stimulating factor and tumour necrosis factor on human hair follicle growth in vitro: a possible role for interleukin-1 and tumour necrosis factor-α in alopecia areataBritish Journal of Dermatology, 1996
- The Insulin-like Growth Factor 1 Receptor Is Expressed by Epithelial Cells with Proliferative Potential in Human Epidermis and Skin Appendages: Correlation of Increased Expression with Epidermal HyperplasiaJournal of Investigative Dermatology, 1996