A peptoid interleukin-15 receptor antagonist suppresses inflammation and arthritis in mice

Kwang Bog Cho, Satya Prakash Shukla, Maheshkumar Kannan, Haowen Zhang, Sundus Jabeen Amina, Shuang Zhou, Yanping Chen, Jeremiah F. Molligan, Veena Taneja, Chandra Mohan, D. Gomika Udugamasooriya, Bin Guo

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To discover a novel peptoid antagonist that targets the interleukin-15 (IL-15) receptor and to evaluate its therapeutic efficacy in the treatment of inflammation and arthritis. Methods: A new compound (IFRA3, interleukin-15 receptor antagonist 3) was discovered using a unique on-bead two-colour combinatorial cell screening of a peptoid library. The interaction of IFRA3 with IL-15 receptor was assessed by in vitro pull-down and thermal shift assays. The efficacy of IFRA3 in treating inflammation and arthritis was evaluated in mouse models. Results: IFRA3Q1 (a tetrameric derivative of IFRA3) inhibited the activity of IL-15 and suppressed CTLL-2 cell proliferation (which depends on IL-15 activity). IFRA3Q1 exhibited strong in vivo anti-inflammatory activity in carrageenan-induced inflammation in mice. Furthermore, IFRA3Q1 inhibited collagen-induced arthritis in DBA/1J mice. Conclusion: By binding to and inhibiting the function of IL-15 receptor, IFRA3Q1 exhibited significant anti-arthritis activity. Our findings suggest that IFRA3Q1 represents a new paradigm for arthritis therapy by targeting IL-15 signalling.

Original languageEnglish (US)
Article numbere1432
JournalClinical and Translational Immunology
Volume11
Issue number11
DOIs
StatePublished - 2022

Keywords

  • inflammation
  • interleukin-15
  • peptoid
  • rheumatoid arthritis

ASJC Scopus subject areas

  • Nursing(all)
  • Immunology and Allergy
  • Immunology

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