An approach to increase the gut-derived maternal immunoglobulin A (IgA) production using dietary tryptophan via aryl hydrocarbon receptor

2020 Fiscal Year Research-status Report

• Project/Area Number: 20K15478
• Research Institution: Tohoku University
• Principal Investigator: イスラム ジャヒドゥル 東北大学, 農学研究科, 特任助教 (20805569)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: Tryptophan / IgA

Outline of Annual Research Achievements

Overall research achievement of this project is excellent. I have found how tryptophan diet changed the microbial composition during early and late stage pregnancy's and overall immunoglobulin A (IgA) secretion is changed. Initially, I found that tryptophan oral gavage produced the microbiome Ruminococcus flavefaciences that actively use tryptophan and produce tryptophan ligands for aryl hydrocarbon receptor (AHR) and tryptophan oral gavege changed the microbial alpha diversity but not the beta diversity. Then, I found how neonatal IgA production is also depended on the maternal IgA. I also found that tryptophan rich diet activated aryl hydrocarbon receptor (AHR) pathway more effectively rather than AHR ligand (indole 3- carbinol) based diet itself through examining the AHR expression in mouse model through investigating the mature B cell and IgA producing plasma cell. However, in cell culture experiment I have AHR ligand downregulated the IgA production. I have checked innate lymphoid cells (ILCs) production in mother (large intetine, mammary gland) and the offspring (milk), however until now I have found that it is independent to the diet. Using the mono clonal antibody system, I have that IgA production is depended on the dose of the tryptophan diet, however ligand based diet is dose independent.

Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

Overall status is satisfactory and I completed necessary experiments that I planned.

Strategy for Future Research Activity

Now I will focus how maternal immunity, a form of passive immunity, helps to protect the neonate during the critical transition from the protected uterine environment of the fetus to the hostile external environment of the newborn. Not only does how this transition occur at a time when the neonate's immune system is not fully developed but also at a time when the neonate's immune system is naive to virtually all pathogens.