Suomeksi
 
 
Microbiota and gut immune system in the pathogenesis of type 1 diabetes

​Description of Research

Our aim is to identify novel mechanisms which link gut immune system to the pathogenesis of type 1 diabetes using the nonobese diabetic (NOD) mouse model. In addition, we collaborate with proteomics and bioinformatics researchers to set up a novel method to investigate how certain functional properties of microbiota affect the diversity of the developing microbiota in the child. Together with researchers in clinical trials, we investigate if these functional properties affect diabetes risk and other health parameters. 

We recently found that the presence of two common dietary fibers in the early diet of newly weaned mice induce abrupt colonization of the gut with a narrow spectrum of microbes, and increase diabetes development in the NOD mouse. We now focus on innate and adaptive immune responses in the distal gut, and have identified three “novel” lymph nodes of the colon, in which also diabetogenic T cells are activated in situ. We continue to investigate how gut microbiome and its composition affect gut homeostasis and dendritic cell – T-cell interactions in these lymph nodes, and identify drug targets to temper the effects of narrow microbial spectrum or “dysbiosis” on adaptive immune responses.

With clinical investigators of the DIPP and FinnBrain studies, we determine if the ability of gut microbes to digest fibers is linked to the development of microbial diversity during the first year of life and to type 1 diabetes or other health.

In collaboration, we are also investigating biomarkers in graft-versus host disease and MS disease, and provide tailored test for the diagnosis of immunodeficiencies for diagnostic and research purposes.

Members of the research group

Raine Toivonen, Ph.D. (Academy of Finland postdoctoral research fellow).
Rohini Emani, M.Sc. (PhD-student)
Ella Kyläinpää, B.Sc. (master’s thesis student)
Hilla Muraja, B.Sc. (master’s thesis student)
Markku Oksman (MD, PhD-student; shared with hematology unit)

Selected Publications

Hänninen A, Toivonen R. On the role of gut bacteria and infant diet in the develop-ment of autoimmunity for type 1 diabetes. Diabetologia 58:2195-6, 2015.

Toivonen R, Arstila TP, Hänninen A. Islet-associated T-cell receptor-β CDR se-quence repertoire in prediabetic NOD mice reveals antigen-driven T-cell expansion and shared usage of VβJβ TCR chains. Mol Immunol. 64:127-35, 2015.

Toivonen RK, Emani R, Munukka E, Rintala A, Laiho A, Pietilä S, Pursiheimo JP, Soidinsalo P, Linhala M, Eerola E, Huovinen P, Hänninen A. Fermentable fibres condition colon microbiota and promote diabetogenesis in NOD mice. Diabetologia 57:2183-2192, 2014.

Emani R, Asghar MN, Toivonen R, Lauren L, Söderström M, Toivola DM, van Tol EA, Hänninen A. Casein hydrolysate diet controls intestinal T cell activation, free radical production and microbial colonisation in NOD mice. Diabetologia 56:1781-1791, 2013.

Alam C, Valkonen S, Palagani V, Jalava J, Eerola E, Hänninen A. Inflammatory tendencies and over production of IL-17 in the colon of young NOD mice are coun-teracted with diet change. Diabetes 59:2237-2246; 2010.

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 Research Group

 
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