Loss of microbiota depletes cross-reactive Foxp3+ Tregs leading to selective immunopathologies
- Published
- Accepted
- Subject Areas
- Immunology
- Keywords
- Foxp3, Allergy, Autoimmunity, Tumor immunology, Vaccine, Microbiota, Immunotherapy, Regulatory T cell, Cross-reactivity
- Copyright
- © 2017 Kamala et al.
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ Preprints) and either DOI or URL of the article must be cited.
- Cite this article
- 2017. Loss of microbiota depletes cross-reactive Foxp3+ Tregs leading to selective immunopathologies. PeerJ Preprints 5:e3237v1 https://doi.org/10.7287/peerj.preprints.3237v1
Abstract
The 'Hygiene hypothesis', a cornerstone model to account for the role of exogenous pathogens and later of endogenous microbiota in immune disorders, is currently presumed to operate at the innate immunity and metabolite levels to properly 'educate' the immune system. Doing so however fails to satisfactorily account for the antigen-specific nature of such disorders. SPIRAL is a novel interpretive framework that resolves this dilemma. It represents the periodic table of cross-reactive Foxp3+ regulatory T cell (Treg) epitopes selected from commensal microbiota over evolutionary time to mediate self-nonself discrimination and effector class regulation. Here, we utilize the SPIRAL's predictive power to provide a mechanistic antigen-specific basis for the initiation of allergies and autoimmune diseases as well as for the failure to mount effective anti-tumor and vaccine responses through selective loss of microbiota and corresponding cross-reactive Foxp3+ Tregs.
Author Comment
This is a practical guide to SPIRAL, a novel interpretive framework that explains the role of the Treg-microbiota axis in selective immunopathologies.