Life-extended glycosylated IL-2 promotes Treg induction and suppression of autoimmunity

Abstract IL-2 is the master-regulator cytokine for T cell dependent responses and is crucial for proliferation and survival of T cells. However, IL-2-based treatments remained marginal, in part due to short half-life. Thus, we aimed to extend IL-2 half-life by flanking the IL-2 core with sequences d...

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Autores principales:	Aner Ottolenghi, Priyanka Bolel, Rhitajit Sarkar, Yariv Greenshpan, Muhammed Iraqi, Susmita Ghosh, Baisali Bhattacharya, Zoe V. Taylor, Kiran Kundu, Olga Radinsky, Roi Gazit, David Stepensky, Ron N. Apte, Elena Voronov, Angel Porgador
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ad6cc7eb08a2453fb99bf074bf0f2812
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spelling	oai:doaj.org-article:ad6cc7eb08a2453fb99bf074bf0f28122021-12-02T14:20:43ZLife-extended glycosylated IL-2 promotes Treg induction and suppression of autoimmunity10.1038/s41598-021-87102-42045-2322https://doaj.org/article/ad6cc7eb08a2453fb99bf074bf0f28122021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87102-4https://doaj.org/toc/2045-2322Abstract IL-2 is the master-regulator cytokine for T cell dependent responses and is crucial for proliferation and survival of T cells. However, IL-2-based treatments remained marginal, in part due to short half-life. Thus, we aimed to extend IL-2 half-life by flanking the IL-2 core with sequences derived from the extensively glycosylated hinge region of the NCR2 receptor. We termed this modified IL-2: “S2A”. Importantly, S2A blood half-life was extended 14-fold compared to the clinical grade IL-2, Proleukin. Low doses inoculation of S2A significantly enhanced induction of Tregs (CD4+ Regulatory T cells) in vivo, as compared to Proleukin, while both S2A and Proleukin induced low levels of CD8+ T cells. In a B16 metastatic melanoma model, S2A treatment was unable to reduce the metastatic capacity of B16 melanoma, while enhancing induction and recruitment of Tregs, compared to Proleukin. Conversely, in two autoimmune models, rheumatoid arthritis and DSS-induced colitis, S2A treatment significantly reduced the progression of disease compared to Proleukin. Our results suggest new avenues for generating long-acting IL-2 for long-standing treatment and a new technique for manipulating short-life proteins for clinical and research uses.Aner OttolenghiPriyanka BolelRhitajit SarkarYariv GreenshpanMuhammed IraqiSusmita GhoshBaisali BhattacharyaZoe V. TaylorKiran KunduOlga RadinskyRoi GazitDavid StepenskyRon N. ApteElena VoronovAngel PorgadorNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Aner Ottolenghi Priyanka Bolel Rhitajit Sarkar Yariv Greenshpan Muhammed Iraqi Susmita Ghosh Baisali Bhattacharya Zoe V. Taylor Kiran Kundu Olga Radinsky Roi Gazit David Stepensky Ron N. Apte Elena Voronov Angel Porgador Life-extended glycosylated IL-2 promotes Treg induction and suppression of autoimmunity
description	Abstract IL-2 is the master-regulator cytokine for T cell dependent responses and is crucial for proliferation and survival of T cells. However, IL-2-based treatments remained marginal, in part due to short half-life. Thus, we aimed to extend IL-2 half-life by flanking the IL-2 core with sequences derived from the extensively glycosylated hinge region of the NCR2 receptor. We termed this modified IL-2: “S2A”. Importantly, S2A blood half-life was extended 14-fold compared to the clinical grade IL-2, Proleukin. Low doses inoculation of S2A significantly enhanced induction of Tregs (CD4+ Regulatory T cells) in vivo, as compared to Proleukin, while both S2A and Proleukin induced low levels of CD8+ T cells. In a B16 metastatic melanoma model, S2A treatment was unable to reduce the metastatic capacity of B16 melanoma, while enhancing induction and recruitment of Tregs, compared to Proleukin. Conversely, in two autoimmune models, rheumatoid arthritis and DSS-induced colitis, S2A treatment significantly reduced the progression of disease compared to Proleukin. Our results suggest new avenues for generating long-acting IL-2 for long-standing treatment and a new technique for manipulating short-life proteins for clinical and research uses.
format	article
author	Aner Ottolenghi Priyanka Bolel Rhitajit Sarkar Yariv Greenshpan Muhammed Iraqi Susmita Ghosh Baisali Bhattacharya Zoe V. Taylor Kiran Kundu Olga Radinsky Roi Gazit David Stepensky Ron N. Apte Elena Voronov Angel Porgador
author_facet	Aner Ottolenghi Priyanka Bolel Rhitajit Sarkar Yariv Greenshpan Muhammed Iraqi Susmita Ghosh Baisali Bhattacharya Zoe V. Taylor Kiran Kundu Olga Radinsky Roi Gazit David Stepensky Ron N. Apte Elena Voronov Angel Porgador
author_sort	Aner Ottolenghi
title	Life-extended glycosylated IL-2 promotes Treg induction and suppression of autoimmunity
title_short	Life-extended glycosylated IL-2 promotes Treg induction and suppression of autoimmunity
title_full	Life-extended glycosylated IL-2 promotes Treg induction and suppression of autoimmunity
title_fullStr	Life-extended glycosylated IL-2 promotes Treg induction and suppression of autoimmunity
title_full_unstemmed	Life-extended glycosylated IL-2 promotes Treg induction and suppression of autoimmunity
title_sort	life-extended glycosylated il-2 promotes treg induction and suppression of autoimmunity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ad6cc7eb08a2453fb99bf074bf0f2812
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Life-extended glycosylated IL-2 promotes Treg induction and suppression of autoimmunity

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