Regulation of thymic T-cell development by intestinal microbiota
| Autor: | Shubhabrata Majumdar, Daniel Zegarra Ruiz, Wan-Jung Wu, Stephanie Orozco, Maria Bettini, Gretchen Diehl, Matthew L. Bettini |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 204:84.5-84.5 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Host commensal microbiota plays an important role in the development and functioning of a healthy immune system. Early life interference with commensal colonization is associated with immune disorders like inflammatory bowel disease (IBD), asthma, allergic rhinitis and atopic dermatitis. One important aspect of microbiota mediated immune regulation is its impact on T-cell differentiation and function. Although most studies show that microbial regulation of T-cells is limited to the periphery, some studies have suggested that the microbiota might impact antigen specific T-cell development in the thymus. However, there has been insufficient data. Interestingly, we are able to detect bacterial signatures by 16s sequencing within mouse and human thymus. Additionally, we observed development of antigen specific thymocytes in SFB colonized 7B8 TCR transgenic mice and in wildtype mice through SFB tetramer staining. We therefore, hypothesize that antigen-presenting cells (APCs) from the gut sample local microbial antigens and migrate to the thymus to present them to the developing thymocytes and influence selection. To test this hypothesis, we tracked the migration of intestinal APCs to the thymus using mice that express the photoconvertible Kikume protein. We performed targeted photo-conversion of the cecum through live surgery and discovered photoconverted APCs in the thymus 48 hours later. These observations open up the possibility that intestinal APCs migrate to the thymus early in life to shape the microbiota specific TCR repertoire. |
| Databáze: | OpenAIRE |
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