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

doi:10.1002/cti2.1432

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

Immunology

Research output: Contribution to journal › Article › peer-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 language	English (US)
Article number	e1432
Journal	Clinical and Translational Immunology
Volume	11
Issue number	11
DOIs	https://doi.org/10.1002/cti2.1432
State	Published - 2022

Keywords

inflammation
interleukin-15
peptoid
rheumatoid arthritis

ASJC Scopus subject areas

General Nursing
Immunology and Allergy
Immunology

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10.1002/cti2.1432

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title = "A peptoid interleukin-15 receptor antagonist suppresses inflammation and arthritis in mice",

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.",

keywords = "inflammation, interleukin-15, peptoid, rheumatoid arthritis",

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

note = "Publisher Copyright: {\textcopyright} 2022 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd, on behalf of Australian and New Zealand Society for Immunology, Inc.",

year = "2022",

doi = "10.1002/cti2.1432",

language = "English (US)",

volume = "11",

journal = "Clinical and Translational Immunology",

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T1 - A peptoid interleukin-15 receptor antagonist suppresses inflammation and arthritis in mice

AU - Cho, Kwang Bog

AU - Shukla, Satya Prakash

AU - Kannan, Maheshkumar

AU - Zhang, Haowen

AU - Amina, Sundus Jabeen

AU - Zhou, Shuang

AU - Chen, Yanping

AU - Molligan, Jeremiah F.

AU - Taneja, Veena

AU - Mohan, Chandra

AU - Udugamasooriya, D. Gomika

AU - Guo, Bin

PY - 2022

Y1 - 2022

N2 - 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.

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

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Keywords

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