Commensal bacteria present in the gastrointestinal tract provide beneficial roles for the host, such as supporting nutrient metabolism. In order to peacefully co-exist with the intestinal microflora the immune system has evolved multiple mechanisms through which it suppresses inflammatory immune responses against commensal bacteria, which together generate a tolerogenic environment. A breakdown in this tolerance can result in the onset of chronic inflammatory disorders such as Inflammatory Bowel Disease (and colon cancer), hepatitis, and rheumatoid arthritis.
Innate lymphoid cells (ILCs) play key roles in mediating intestinal immune homeostasis and maintaining healthy host-commensal bacteria interactions via the production of cytokines, interactions with other tissue-resident immune cell populations and the orchestration of local immune responses. In particular, recent studies have demonstrated that group 3 innate lymphoid cells are able to prevent intestinal inflammation by controlling the activation of commensal bacteria-specific inflammatory T cells in an antigen-specific manner (Hepworth et al Nature 2013, Science 2015).
This project will investigate i) how ILCs interact with intestinal immune cells to regulate responses to commensal bacteria ii) which bacterial species preferentially drive intestinal inflammation following disruption of ILC regulatory function(s) and iii) the specificity of ILC-regulation of inflammatory responses.
The project will utilize a range of approaches including the use of animal models, immunological techniques (flow cytometry, ELISA), molecular biology (PCR, sequencing) and microbiological methods to investigate interactions between the host immune system and the commensal microbiota in the context of health and disease.
The student will my join my laboratory located within the world-class Faculty of Life Sciences at the University of Manchester and will have access to a wide range of facilities and expertise across the faculty.
- Hooper LV, Littman DR and MacPherson AJ. Interactions between the microbiota and the immune system. Science 2012 June 8; 336(6086)
- Belkaid Y and Hand TW. Role of the microbiota in immunity and inflammation. Cell 2014 Mar 27; 157(1)
- Hepworth MR et al Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4+ T cells Science 2015 May 29; 348(6238)
- Hepworth MR et al Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria Nature 2013 Jun 6; 498(7452)
- Palm NW et al Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease Cell 2014 Aug 28; 158(5)