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Updated: Aug 19, 2025

An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
A peptoid interleukin-15 receptor antagonist suppresses inflammation and arthritis in mice
Kwang Bog Cho1, Satya Prakash Shukla1, Maheshkumar Kannan1
1Department of Pharmacological and Pharmaceutical Sciences University of Houston Houston TX USA.
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.
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