2. Academic Validation
  3. Activation of NF-κB signaling in tissue-resident memory T cells promotes recurrent psoriasis in mice

Activation of NF-κB signaling in tissue-resident memory T cells promotes recurrent psoriasis in mice

  • Front Immunol. 2026 Feb 9:16:1762269. doi: 10.3389/fimmu.2025.1762269.
Yukang Lin # 1,  Jiaying Chen # 1,  Han Du # 2,  Yuchao Chen 1,  Zhaolin Liu 1,  Xuejia Li 1,  Yongdan Li 1,  Feifei Qiu 1,  Lingling Wen 3,  Siyuan Xu 4 5,  Huazhen Liu 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
  • 2 Maoming Hospital of Guangzhou University of Chinese Medicine, Maoming, China.
  • 3 Shenzhen Traditional Chinese Medical Hospital, Shenzhen, China.
  • 4 The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
  • 5 Sci-tech Industrial Park of Guangzhou University of Chinese Medicine, Guangzhou, China.
  • # Contributed equally.
PMID: 41737494 DOI: 10.3389/fimmu.2025.1762269
Abstract

Background: Recurrence triggered by immunological memory is a critical challenge in the treatment of psoriasis. Tissue-resident memory T (Trm) cells are the primary pacemakers in recurrent psoriasiform dermatitis following stimulation and Infection by previous pathogens. However, the mechanisms underlying Trm cell activation remain unclear.

Methods: In this study, imiquimod-induced recurrent psoriatic mice were established to characterize the phenotypes of different Trm cell subsets. CD8+/CD4+ Tcm cell injection and NF-κB Inhibitor or agonist treatment were then used to investigate the role and mechanisms of Trm cells in recurrent psoriasis. Finally, CD8+ T cells and keratinocyte co-culture systems were established to investigate the effects of activating NF-κB activation in Trm cells.

Results: Mice displayed severe psoriatic dermatitis after repeated imiquimod treatment. The CD8+ Trm cells, but not CD4+ Trm cells, were elevated in the skin of recurrent psoriatic mice. Injection of CD8+ Tcm cells injection elicited more severe psoriatic symptoms than imiquimod treatment alone, indicating that CD8+ Trm cells are critical participants in psoriatic recurrence. Phosphorylation of NF-kB p65 (RELA), p-IKKa, p-RelB and NF-kB p100/p52 was enhanced in the skin of imiquimod-induced recurrent psoriatic mice. NF-κB Inhibitor/agonist treatment significantly suppressed or restored the dermatitis severity and CD8+ Trm cell levels in recurrent psoriatic mice. Meanwhile, NF-κB inhibition also restored the expression of DLAT in Trm cells. Finally, NF-κB inhibitors directly suppressed Trm cell activation and inflammation of Trm cells in vitro.

Conclusion: Together, these findings suggest that canonical and non-canonical NF-κB signaling directly activates Trm cell differentiation, inhibits cellular Cuproptosis, and promotes recurrent psoriasis.

Keywords

NF-κB signaling; imiquimod; inflammation; recurrent psoriasis; tissue resident memory T cells.

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