p19-targeted ABD-derived protein variants inhibit IL-23 binding and exert suppressive control over IL-23-stimulated expansion of primary human IL-17+T-cells

Křížová, Lucie; Kuchař, Milan; Petroková, Hana; Osička, Radim; Hlavničková, Marie; Pelák, O.; Černý, Jiří; Kalina, T.; Malý, Petr

doi:https://dx.doi.org/10.1080/08916934.2016.1272598

Number of the records: 1

p19-targeted ABD-derived protein variants inhibit IL-23 binding and exert suppressive control over IL-23-stimulated expansion of primary human IL-17+T-cells

1.

SYSNO ASEP	0474402
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	p19-targeted ABD-derived protein variants inhibit IL-23 binding and exert suppressive control over IL-23-stimulated expansion of primary human IL-17+T-cells
Author(s)	Křížová, Lucie (BTO-N) Kuchař, Milan (BTO-N)_RID Petroková, Hana (BTO-N)_RID Osička, Radim (MBU-M)_{RID, ORCID} Hlavničková, Marie (BTO-N) Pelák, O. (CZ) Černý, Jiří (BTO-N)_{RID, ORCID} Kalina, T. (CZ) Malý, Petr (BTO-N)_{RID, ORCID}
Number of authors	9
Source Title	Autoimmunity - ISSN 0891-6934 Roč. 50, č. 2 (2017), s. 102-113
Number of pages	12 s.
Language	eng - English
Country	GB - United Kingdom
Keywords	Psoriasis ; Th17 cell ; IL-23 ; protein binder
Subject RIV	EC - Immunology
OECD category	Immunology
Subject RIV - cooperation	Institute of Microbiology - Immunology
R&D Projects	NV16-27676A GA MZd - Ministry of Health (MZ)
	GAP303/10/1849 GA ČR - Czech Science Foundation (CSF)
	GA15-09157S GA ČR - Czech Science Foundation (CSF)
	ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
Institutional support	BTO-N - RVO:86652036 ; MBU-M - RVO:61388971
UT WOS	000395557200004
EID SCOPUS	85009968778
DOI	10.1080/08916934.2016.1272598
Annotation	Interleukin-23 (IL-23), a heterodimeric cytokine of covalently bound p19 and p40 proteins, has recently been closely associated with development of several chronic autoimmune diseases such as psoriasis, psoriatic arthritis or inflammatory bowel disease. Released by activated dendritic cells, IL-23 interacts with IL-23 receptor (IL-23R) on Th17 cells, thus promoting intracellular signaling, a pivotal step in Th17-driven pro-inflammatory axis. Here, we aimed to block the binding of IL-23 cytokine to its cell-surface receptor by novel inhibitory protein binders targeted to the p19 subunit of human IL-23. To this goal, we used a combinatorial library derived from a scaffold of albumin-binding domain (ABD) of streptococcal protein G, and ribosome display selection, to yield a collection of ABD-derived p19-targeted variants, called ILP binders. From 214 clones analyzed by ELISA, Western blot and DNA sequencing, 53 provided 35 different sequence variants that were further characterized. Using in silico docking in combination with cell-surface competition binding assay, we identified a group of inhibitory candidates that substantially diminished binding of recombinant p19 to the IL-23R on human monocytic THP-1 cells. Of these best p19-blockers, ILP030, ILP317 and ILP323 inhibited IL-23-driven expansion of IL-17-producing primary human CD4(+)T-cells. Thus, these novel binders represent unique IL-23-targeted probes useful for IL-23/IL-23R epitope mapping studies and could be used for designing novel p19/IL-23-targeted anti-inflammatory biologics.
Workplace	Institute of Biotechnology
Contact	Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700
Year of Publishing	2018

Number of the records: 1