4 years ago

Empirical modeling of T cell activation predicts interplay of host cytokines and bacterial indole

Empirical modeling of T cell activation predicts interplay of host cytokines and bacterial indole
Shelby Steinmeyer, Arul Jayaraman, Juergen Hahn, Robert C. Alaniz, Daniel P. Howsmon
Adoptive transfer of anti-inflammatory FOXP3+ Tregs has gained attention as a new therapeutic strategy for auto-inflammatory disorders such as Inflammatory Bowel Disease. The isolated cells are conditioned in vitro to obtain a sufficient number of anti-inflammatory FOXP3+ Tregs that can be reintroduced into the patient to potentially reduce the pathologic inflammatory response. Previous evidence suggests that microbiota metabolites can potentially condition cells during the in vitro expansion/differentiation step. However, the number of combinations of cytokines and metabolites that can be varied is large, preventing a purely experimental investigation which would determine optimal cell therapeutic outcomes. To address this problem, a combined experimental and modeling approached is investigated here: an artificial neural network model was trained to predict the steady-state T cell population phenotype after differentiation with a variety of host cytokines and the microbial metabolite indole. This artificial neural network model was able to both reliably predict the phenotype of these T cell populations and also uncover unexpected conditions for optimal Treg differentiation that were subsequently verified experimentally. Biotechnol. Bioeng. 2017;9999: 1–8. © 2017 Wiley Periodicals, Inc. Empirical modeling of T cell differentiation predicts anti-inflammatory effects of the bacterial metabolite indole. Additionally, novel interactions of host cytokines and indole emerge, suggesting stimulation conditions that can be used to simultaneously maximize differentiation toward anti-inflammatory Tregs and minimize pro-inflammatory Th17 cells. This work highlights the utility of incorporating bacterial signals such as indole in the differentiation step prior to transplantation in T cell adoptive transfer.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/bit.26371

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.