Dimeric translationally controlled tumor protein-binding peptide 2 attenuates imiquimod-induced psoriatic inflammation through induction of regulatory T cells

Biomed Pharmacother. 2022 Aug;152:113245. doi: 10.1016/j.biopha.2022.113245. Epub 2022 Jun 8.

Abstract

Psoriasis is a chronic skin inflammation caused by a dysfunctional immune system, which causes systemic inflammation in various organs and tissues. Due to the risk of systemic inflammation and recurrence of psoriasis, it is important to identify the critical targets in the pathogenesis of psoriasis and develop targeted therapeutics. Dimerized translationally controlled tumor protein (dTCTP) promotes immune cell activation as a pro-inflammatory cytokine and plays a role in developing allergic diseases such as asthma and rhinitis. Here, we sought to explore whether dTCTP and its inhibition contributed to the development and control of imiquimod (IMQ)-induced psoriasis. Topical application of IMQ inflamed the skin of the back and ear, increased inflammatory cytokines, and decreased regulatory T cell markers. Interestingly, TCTP was significantly increased in inflamed skin and immune cells such as T cells, B cells, and macrophages after IMQ treatment and was secreted into the serum to undergo dimerization. Extracellular dTCTP treatment selectively suppressed regulatory T (Treg) cells, not other effector T helper (Th) cells, and increased M1 macrophages. Moreover, dTCTP-binding peptide 2 (dTBP2), a dTCTP inhibitor peptide, effectively attenuated the systemic inflammatory responses, including Th17 cell response, and alleviated psoriatic skin inflammation. dTBP2 blocked dTCTP-mediated Treg suppression and stimulated the expression of Treg cell markers in the spleen and inflammatory skin lesions. These results suggest that dTCTP dysregulated immune balance through Treg suppression in psoriatic inflammation and that functional inhibition of dTCTP by dTBP2 maintained immune homeostasis and attenuated inflammatory skin diseases by expanding Treg cells.

Keywords: DTBP2; Effector Th cells; IMQ; M1 macrophages; Psoriasis; TCTP; Treg cells.

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Disease Models, Animal
  • Imiquimod / pharmacology
  • Inflammation / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Peptides / pharmacology
  • Psoriasis* / chemically induced
  • Psoriasis* / drug therapy
  • Skin
  • T-Lymphocytes, Regulatory* / metabolism
  • Th17 Cells
  • Tumor Protein, Translationally-Controlled 1

Substances

  • Cytokines
  • Peptides
  • Tumor Protein, Translationally-Controlled 1
  • Imiquimod