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IL-17A causes depression-like symptoms via NFκB and p38MAPK signaling pathways in mice: Implications for psoriasis associated depression
Abstract
Psoriasis has been shown to be associated with an increased prevalence of comorbid major depression. IL-17A plays an important role in both depression and psoriasis. IL-17A has been shown to be elevated in systemic circulation of psoriatic patients. IL-17A released from different immune cells during psoriasis may be responsible for the development of neuropsychiatric symptoms associated with depression. Therefore, this study explored the association of systemic IL-17A with depression. The present study utilized imiquimod model of psoriatic inflammation as well as IL-17A administration in mice to investigate the effect of IL-17A on depression-like behavior. Psoriatic inflammation led to enhanced IL-17A expression in peripheral immune cells of both innate and adaptive origin. This was associated with increased NFκB/p38MAPK signaling and inflammatory mediators in different brain regions, and depression-like symptoms (as reflected by sucrose preference and tail suspension tests). The role of IL-17A was further confirmed by administering it alone for ten days, followed by assessment of the same parameters. IL-17A administration produced effects similar to psoriasis-like inflammation on neurobehavior and NFκB/p38MAPK pathways. Moreover, both NFκB and p38MAPK inhibitors led to attenuation in IL-17A associated with depression-like behavior via reduction in inflammatory mediators, such as MCP-1, iNOS, IL-6, and CXCL-2. Furthermore, anti-IL17A antibody also led to a reduction in imiquimod-induced depression-like symptoms, as well as NFκB/p38MAPK signaling. The present study shows that IL-17A plays an important role in comorbid depression associated with psoriatic inflammation, where both NFκB and p38MAPK pathways play significant roles via upregulation of inflammatory mediators in the brain.
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“The sustained activation of the IL-17 pathway in chronic social defeat stress conditions suggests a maladaptive neuroimmune response, which may underlie the persistent behavioral changes observed”
From Comparative Analysis of HPA-Axis Dysregulation and Dynamic Molecular Mechanisms in Acute Versus Chronic Social Defeat Stress (2025) · cites this paper as [48]
In the citing paper
“Preclinical studies in rodents corroborate these findings, showing that IL-17A administration induces depressive-like behaviors [48] and stress exposure elevates IL-17A levels [66,67,68,69].”
From Comparative Analysis of HPA-Axis Dysregulation and Dynamic Molecular Mechanisms in Acute Versus Chronic Social Defeat Stress (2025) · cites this paper as [48]
In the citing paper
“administration of IL-17A in rodents promotes depressive-like behaviors (Nadeem et al., 2017)”
From Distinct characteristics of hippocampal pathogenic th17 cells in a mouse model of depression (2018) · cites this paper as Nadeem et al., 2017
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Metadata
- Authors
- Nadeem, A., Ahmad, S. F., Al-Harbi, N. O., Fardan, A. S., El-Sherbeeny, A. M., Ibrahim, K. E., & Attia, S. M.
- Affiliations
- King Saud University (SA)
- Corresponding author
- Nadeem, Ahmed
- Venue
- Cytokine
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 97
- Pages
- 14-24
- ISSN
- 1043-4666 (ISSN-L)
- OpenAlex
- W2617690685
- Cited by
- 147
- References
- 54
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 10 · 2023: 31 · 2022: 24 · 2021: 18 · 2020: 14 · 2019: 6 · 2018: 14 · 2017: 2
- FWCI
- 3.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cytokine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deanship of Scientific Research at King Saud University (RG-1438-019)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- IL-17A, depression-like behavior, psoriasis, NF-κB signaling, p38 MAPK signaling, neuroinflammation, anti-IL-17A antibody, comorbid depression
- MeSH terms
- Imiquimod, Aminoquinolines, Animals, Brain, Depression, Major Depressive Disorder, Depressive Disorder, Major, Disease Models, Animal, Humans, Inflammation, Psoriasis, NF-kappa B, Interleukin-17, MAP Kinase Signaling System, p38 Mitogen-Activated Protein Kinases, Mice
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