Lactobacillus delivery of bioactive interleukin-22

Lin, Yinyao; Krogh-Andersen, Kasper; Hammarström, Lennart; Marcotte, Harold

doi:10.1186/s12934-017-0762-1

Cited by 14 publications

(12 citation statements)

References 35 publications

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“…Previous groups have shown the ability to produce IL-22 and we suspect they had similar problems with IL-22 toxicity that we observed in our study. Expression of hIL-22 from L. lactis (2-20 ng/ml) showed 50-500 fold less IL-22 protein than what we report here as well as mIL-22 (L. plantarum, 500 ng/ml) (Loera-Arias et al, 2014;Lin et al, 2017). The low levels of hIL-22 production in L. lactis and our work showing cleavage of hIL-22 in L. lactis when hIL-22 levels are much higher suggest that hIL-22 also has a negative impact on L. lactis.…”

Section: Discussioncontrasting

confidence: 59%

“…Previous work on creating bacterial delivery systems for the secretion of human and mouse IL-22 have mainly tested in vitro activity by measuring the production of IL-10 from Colo205 cells (Loera-Arias et al, 2014;Lin et al, 2017). This assay, however, might not necessarily reflect the ability of hIL-22 to strengthen mucosal immunity at epithelial surfaces and promote tissue repair, effects that are essential to achieving its therapeutic effect in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…We subsequently assessed the biological activity of hIL-22 secreted by PRB484. The production of IL-10 and the phosphorylation of STAT3 (pSTAT3) in the cell culture line Colo205 in the presence of hIL-22 are commonly used assays to demonstrate the activity of this protein (Nagalakshmi et al, 2004;Loera-Arias et al, 2014;Lin et al, 2017). To investigate if hIL-22 secreted by L. reuteri 6475 was biologically active, we incubated Colo205 cells with commercial recombinant hIL-22 (rhIL-22), supernatants from PBR484 or L. reuteri harboring pSIP411 as a negative control (PRB577).…”

Section: Biological Activity Of Hil-22 Produced By L Reuterimentioning

confidence: 99%

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Challenges and Pitfalls in the Engineering of Human Interleukin 22 (hIL-22) Secreting Lactobacillus reuteri

Ortiz-Velez

Goodwin

Schaefer

et al. 2020

Front. Bioeng. Biotechnol.

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Engineered microbes for the delivery of intestinally directed therapeutics is a promising avenue for the treatment of various intestinal diseases including inflammatory bowel disease (IBD) and intestinal graft vs. host disease (GVHD). This modality of treatment would allow for the targeted delivery of therapeutics to the site of inflammation or disease while minimizing the systemic side effects that often accompany treatment of these pathologies. Here, we show the challenges encountered and overcome in successfully engineering Lactobacillus reuteri to secrete high levels of biologically active human interleukin 22 (hIL-22). Initial hIL-22 constructs secreted high levels of hIL-22, however we found the majority of hIL-22 was cleaved and not biologically active. Several strategies were explored to improve the production of intact hIL-22, with the optimization of the signal sequence for peptide secretion having the most impact of production of intact hIL-22. This resulted in L. reuteri secreting high concentrations (up to 700 ng/mL) of hIL-22. Bioactivity of hIL-22 was confirmed by the secretion of interleukin 10 (IL-10) from the colon cancer derived epithelial cell line Colo205 and the secretion of Regenerating isletderived protein 3 alpha (Reg3α) from human jejunal enteroids. The secretion of bioactive hIL-22 imposed a significant cost for L. reuteri as bacterial growth was significantly impaired upon induction. Future challenges and optimization strategies for the delivery of hIL-22 to the human intestinal tract are discussed.

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Section: Discussioncontrasting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Biological Activity Of Hil-22 Produced By L Reuterimentioning

confidence: 99%

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Challenges and Pitfalls in the Engineering of Human Interleukin 22 (hIL-22) Secreting Lactobacillus reuteri

Ortiz-Velez

Goodwin

Schaefer

et al. 2020

Front. Bioeng. Biotechnol.

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“…Genentech has an IL-22-Fc molecule (UTR1147A) under phase 1 trials with the eventual strategy for short-term use in active IBD patients (90). Probiotic Lactobacillusexpressing IL-22 has been proposed to benefit graft-versus-host disease patients (91). These research directions are still in early stages, and much needs to be done to translate these studies from the laboratory to the clinic.…”

Section: Is Il-22 a Viable Therapeutic Target?mentioning

confidence: 99%

IL-22: There Is a Gap in Our Knowledge

Zenewicz

2018

ImmunoHorizons

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IL-22 is a critical cytokine in modulating tissue responses during inflammation. IL-22 is upregulated in many chronic inflammatory diseases, making IL-22 biology a potentially rewarding therapeutic target. However, this is complicated by the dual-natured role of IL-22 in inflammation, as the cytokine can be protective or inflammatory depending on the disease model. Although scientific interest in IL-22 has increased considerably in the past 10 y, there is still much we do not know about the environmental, cellular, and molecular factors that regulate the production and function of this cytokine. A better understanding of IL-22 biology will allow us to develop new or improved therapeutics for treating chronic inflammatory diseases. In this article, I will highlight some of the outstanding questions in IL-22 biology.

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“…When IL-22 binds to the canonical receptor it can signal increased production of antimicrobial peptides (AMPs), tissue repair proteins and mucous proteins, protecting the host animal from pathogens. IL-22 has recently gained notable attention as a human therapeutic agent both for treatment of infectious or inflammatory diseases (Stefanich et al, 2018;Lekkerkerker et al, 2017;Gao and Xiang, 2018;Tang et al, 2018;Lin, Krogh-Andersen, Hammarström, & Marcotte, 2017) as well as tissue preservation and wound repair (Kolumam et al, 2017). While IL-22 has been expressed successfully in a number of heterologous expression systems (e.g.…”

Section: Introductionmentioning

confidence: 99%

Plant Production and Functional Characterization of Catfish Interleukin 22 as a Natural Immune Stimulant for Aquaculture

Elkins¹,

Dolan²

Authorea

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As the world population increases and wild caught fisheries decline, aquaculture offers an important sustainable solution in addressing this global challenge. However, disease management remains difficult. With limited options, there is a need for innovative solutions. The cytokine interleukin-22 (IL-22) has emerged as a possible therapeutic target for fish and has been correlated with protection under pathogen challenge. Plant-based production systems have the potential to effectively manufacture and bring unique efficacy-enhancing features to the aquaculture industry; namely, the advantages of low cost for this commodity market, ready scalability, and reduced environmental impact. Plant-expressed recombinant cfIL-22 yield and purity were adequate for in vitro activity assessment. This study serves as the first report supporting the use of plants to express therapeutic proteins with application for the aquaculture industry. Bioactivity assays showed cfIL-22 notably increased the proliferation of catfish cells, highlighting the tissue preservation capabilities of this protein. Recombinant cfIL-22 also upregulated expression of genes encoding a tissue repair protein, fibronectin, an antimicrobial peptide, Natural killer lysin-1, and a common innate immune protein, interferon. These findings support plant-made recombinant catfish interleukin-22 as a potential therapeutic for the aquaculture industry and supports further analysis of this protein for therapeutic use.

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Lactobacillus delivery of bioactive interleukin-22

Cited by 14 publications

References 35 publications

Challenges and Pitfalls in the Engineering of Human Interleukin 22 (hIL-22) Secreting Lactobacillus reuteri

Challenges and Pitfalls in the Engineering of Human Interleukin 22 (hIL-22) Secreting Lactobacillus reuteri

IL-22: There Is a Gap in Our Knowledge

Plant Production and Functional Characterization of Catfish Interleukin 22 as a Natural Immune Stimulant for Aquaculture

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