2014 Fiscal Year Annual Research Report
Elucidating the role of IgA in host-bacterial symbiosis in the gut
| Project/Area Number |
25293118
|
|---|
| Research Institution | The Institute of Physical and Chemical Research |
|---|
Principal Investigator |
ファガラサン シドニア 独立行政法人理化学研究所, 統合生命医科学研究センター, チームリーダー (00391970)
|
|---|
| Project Period (FY) |
2013-04-01 – 2016-03-31
|
| Keywords | 免疫学 / IgA |
|---|
| Outline of Annual Research Achievements |
Our aim was to elucidate the contribution of the adaptive immune system to regulating the bacterial communities in the gut. We found that the acquired arm of the immune system, namely the B and T cells are critical to maintain diversity and balance of microbial communities in the gut. In short, we found that Foxp3+ T cells significantly contribute to diversification of gut microbial communities, by preventing the inflammation and regulating the selection of immunoglobulin A. The mice lacking this regulatory control exhibited reduced diversity and unbalanced bacterial communities. Diversified and balanced microbiota in turn feedback to the immune system and induce and maintain its maturation and fitness. The conclusion from this study is that the adaptive immune system mediates host-microbial symbiosis by controlling the richness and balance of bacteria communities through cellular and molecular components required for immune tolerance and selection of antibody repertoire. This is very important finding not only because it explains the co-evolution of the adaptive immune system with bacteria and their reciprocal interactions, but also because it points that microbial dysbiosys associated with inflammation or aging might be initially triggered by deregulated immune responses.
|
| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
During the last two years we have established the know-how required for evaluating the interactions between bacteria and the immune system. We set up all the mice conditions required to address the relevant questions. We also set up FACS protocols for sorting bacteria from diverse regions of the gut. We also established the condition for sorting and characterization of IgA coated bacteria. These already established settings shall allow us to take off rapidly with the planned experiments. We were slightly delayed with the bacteria 16S rRNA gene analyses by that fact that bacteria sequencing platform changed from Roche to Illumina and we needed to set up the optimal primers and condition for such changes. We are currently carefully evaluating the data obtained from preliminary studies, before proceeding with experimental samples. We also established the germ-free colony in order to perform microbial transplantation experiments. We are currently perfecting our techniques to culture bacteria under anaerobic conditions. Other assays to evaluate the mucosal immune function are already established. In summary, the effort put into this project so far should allow a rather smooth continuation of the project.
|
| Strategy for Future Research Activity |
We further aim to elucidate how IgA or the quality and diversity of IgAs affect the composition and localization of bacteria in the gut. Therefore initially we will try to identify the IgA-coated bacteria in different regions-lower part of the small intestine, ceccum or feces-in normal mice. The very simple question is whether similar species of bacteria are coated with IgA or different IgA coated species will be present in different gut segments. Thus we will reveal whether the geography of IgA-bound bacteria along the gastrointestinal tract.
|
| Causes of Carryover |
Reagent from overseas maker was out of stock and was not delivered in time for the experiment.
|
| Expenditure Plan for Carryover Budget |
Purchase reagents.
|
Research Products
(14 results)
-
-
[Journal Article] Foxp3+ T Cells Regulate Immunoglobulin A Selection and Facilitate Diversification of Bacterial Species Responsible for Immune Homeostasis2014
Author(s)
Shimpei Kawamoto, Mikako Maruya, Lucia M. Kato, Wataru Suda, Koji Atarashi, Yasuko Doi, Yumi Tsutsui, Hongyan Qin, Kenya Honda, Takaharu Okada, Masahira Hattori, and Sidonia Fagarasan
-
Journal Title
Immunity
Volume: 41
Pages: 152-165
DOI
Peer Reviewed / Open Access / Acknowledgement Compliant
-
-
-
-
-
-
-
-
-
-
-
-
