Secretion and surface display of binders of IL-23/IL-17 cytokines and their receptors in<i> Lactococcus</i><i> lactis</i> as a therapeutic approach against inflammation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F23%3A00576609" target="_blank" >RIV/86652036:_____/23:00576609 - isvavai.cz</a>

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0928098723001987?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0928098723001987?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejps.2023.106568" target="_blank" >10.1016/j.ejps.2023.106568</a>

Result language

angličtina

Original language name

Secretion and surface display of binders of IL-23/IL-17 cytokines and their receptors in<i> Lactococcus</i><i> lactis</i> as a therapeutic approach against inflammation

Original language description

The cytokine IL-23 activates the IL-23 receptor (IL-23R) and stimulates the differentiation of naive T helper (Th) cells into a Th17 cell population that secretes inflammatory cytokines and chemokines. This IL-23/Th17 proinflammatory axis drives inflammation in Crohn's disease and ulcerative colitis and represents a therapeutic target of monoclonal antibodies. Non-immunoglobulin binding proteins based on the Streptococcus albuminbinding domain (ABD) provide a small protein alternative to monoclonal antibodies. They can be readily expressed in bacteria. Lactococcus lactis is a safe lactic acid bacterium that has previously been engineered as a vector for the delivery of recombinant therapeutic proteins to mucosal surfaces. Here, L. lactis was engineered to display or secrete ABD-variants against the IL-17 receptor (IL-17R). Its expression and functionality were confirmed with flow cytometry using specific antibody and recombinant IL-17R, respectively. In addition, L. lactis were engineered into multifunctional bacteria that simultaneously express two binders from pNBBX plasmid. First, binders of IL-17R were combined with binder of IL-17. Second, binders of IL-23R were combined with binders of IL-23. The dual functionality of the bacteria was confirmed by flow cytometry using corresponding targets, namely the recombinant receptors IL-17R and IL-23R or the p19 subunit of IL-23. Binding of IL17 was confirmed by ELISA. With the latter, 97% of IL-17 was removed from solution by 2 x 109 recombinant bacteria. Moreover, multifunctional bacteria targeting IL-17/IL-17R prevented IL-17A-mediated activation of downstream signaling pathways in HEK-Blue IL-17 cell model. Thus, we have developed several multifunctional L. lactis capable of targeting multiple factors of the IL-23/Th17 proinflammatory axis. This represents a novel therapeutic strategy with synergistic potential for the treatment of intestinal inflammations.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30104 - Pharmacology and pharmacy

Project

<a href="/en/project/GF21-16423K" target="_blank" >GF21-16423K: Small protein blockers of IL-23/IL-17 axis as intestinal inflammation inhibitors secreted by probiotic bacteria.</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

European Journal of Pharmaceutical Sciences

ISSN

0928-0987

e-ISSN

1879-0720

Volume of the periodical

190

Issue of the periodical within the volume

NOV 1 2023

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

10

Pages from-to

106568

UT code for WoS article

001070815000001

EID of the result in the Scopus database

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