1: DOCK2 is involved in the host genetics and biology of severe COVID-19.
Science of the Month - February 2023
Nature.
2022 Sep;609(7928):754-760. doi: 10.1038/s41586-022-05163-5. Epub 2022 Aug 8.
Ho Namkoong, Ryuya Edahiro, Tomomi Takano, Hiroshi Nishihara, Yuya Shirai, Kyuto Sonehara, Hiromu Tanaka, Shuhei Azekawa, Yohei Mikami, Ho Lee, Takanori Hasegawa, Koji Okudela, Daisuke Okuzaki, Daisuke Motooka, Masahiro Kanai, Tatsuhiko Naito, Kenichi Yamamoto, Qingbo S. Wang, Ryunosuke Saiki, Rino Ishihara, Yuta Matsubara, Junko Hamamoto, Hiroyuki Hayashi, Yukihiro Yoshimura, The Biobank Japan Project, …Yukinori Okada
COVID-19 continues to leave a significant mark on society. Led by Takanori Kanai, Dean of the School of Medicine, and Professor Koichi Fukunaga of the Department of Respiratory Medicine, a multi-institutional collaborative research team called the "Japan COVID-19 Task Force" was launched in the early stages of the pandemic. With the participation of over 100 hospitals nationwide, the team has collected clinical samples from over 6,400 COVID-19 patients (as of the end of January 2023) and has grown into the largest research group in Asia in terms of the number of biological samples. Through GWAS, the Japan COVID-19 Task Force discovered that genetic polymorphisms in the DOCK2 gene region, known to play a crucial role in immune function, are associated with the risk of severe disease in non-elderly individuals. Furthermore, through detailed analyses including RNA-seq, single-cell RNA-seq, pathological analysis, cell experiments, and animal experiments, they found that DOCK2 is not only a marker for the severity of COVID-19 but also a therapeutic target for the disease.
(Ho Namkoong, Senior Assistant Professor, Department of Infectious Diseases, 86th graduating class)
2: Microbiota imbalance induced by dietary sugar disrupts immune-mediated protection from metabolic syndrome.
Cell.
2022;185(19):3501-+. [Article]
Kawano Y, Edwards M, Huang YM, Bilate AM, Araujo LP, Tanoue T, Atarashi K, Ladinsky MS, Reiner SL, Wang HH, Mucida D, Honda K, Ivanov, II.
The authors have reported that a proinflammatory shift in intestinal immunity, which is at the forefront of interaction with diet and gut microbiota, is an important initial event in the pathogenesis of obesity and diabetes, triggering intestinal barrier dysfunction and the onset of systemic insulin resistance. Dr. Ivanov's group, where I studied, has reported that the commensal gut bacterium Segmented Filamentous Bacteria (SFB) induces non-inflammatory Th17 cells in the small intestine, which strengthens the intestinal barrier and is crucial for defense against infection. This study revealed that these SFB-induced Th17 cells have the effect of suppressing fat absorption in the small intestine and inhibiting obesity-related enteritis, thereby suppressing the onset of obesity and diabetes. Furthermore, the maintenance of these resident Th17 cells is disrupted by high sucrose intake, which worsens the gut environment and leads to obesity-related enteritis and increased fat absorption. As a preemptive medical approach to suppress the onset of diabetes, we believe that controlling the gut environment by managing high sucrose intake is important, and we intend to pursue further research.
(Yoshinaga Kawano, Department of Nephrology, Endocrinology and Metabolism, 86th graduating class)
3: Cytochrome P450 oxidase 2J inhibition suppresses choroidal neovascularization in mice
Metabolism.
Gong Y*, Tomita Y*, Edin ML, Rena A, Ko M, Yan J, Bull E, Zeldinc DC, Hellstrome A, Fu Z, Smith LEH.
There has been much debate, including large-scale clinical trials, on whether ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) are effective in preventing age-related macular degeneration. LCPUFAs are metabolized through three pathways. We focused on one of these, the CYP2 pathway, and investigated whether we could suppress choroidal neovascularization (CNV), a problem in macular degeneration, by controlling its metabolites. When we induced CNV with a laser in CYP2J-overexpressing mice administered LCPUFAs, the CNV was exacerbated compared to wild-type mice. Furthermore, administering a CYP2J inhibitor (flunarizine) to CNV-induced mice suppressed CNV, and co-administration with a CYP2C inhibitor (montelukast) further enhanced the suppressive effect on CNV. These findings suggest that combining LCPUFA administration with CYP2 inhibitors may be an effective approach to suppressing CNV, providing momentum for the drug repositioning of these existing medications.
(Yohei Tomita, Department of Ophthalmology, equivalent to the 85th graduating class)
Other Publications
1: Longitudinal monitoring of circulating immune cell phenotypes in large vessel vasculitis.
Autoimmunity Reviews.
Matsumoto K, Suzuki K, Yoshida H, Magi M, Kaneko Y, Takeuchi T.
2: AJM300 (carotegrast methyl), an oral antagonist of alpha 4-integrin, as induction therapy for patients with moderately active ulcerative colitis: a multicentre, randomised, double-blind, placebo-controlled, phase 3 study.
Lancet Gastroenterology & Hepatology.
Matsuoka K, Watanabe M, Ohmori T, Nakajima K, Ishida T, Ishiguro Y, Kanke K, Kobayashi K, Hirai F, Watanabe K, Mizusawa H, Kishida S, Miura Y, Ohta A, Kajioka T, Hibi T.
3: Intervention with a humanoid robot avatar for individuals with social anxiety disorders comorbid with autism spectrum disorders.
Asian Journal of Psychiatry.
Yoshida A, Kumazaki H, Muramatsu T, Yoshikawa Y, Ishiguro H, Mimura M.
4: U-shaped association between abnormal serum uric acid levels and COVID-19 severity: reports from the Japan COVID-19 Task Force.
International Journal of Infectious Diseases.
Fukushima T, Chubachi S, Namkoong H, Otake S, Nakagawara K, Tanaka H, Lee H, Morita A, Watase M, Kusumoto T, Masaki K, Kamata H, Ishii M, Hasegawa N, Harada N, Ueda T, Ueda S, Ishiguro T, Arimura K, Saito F, Yoshiyama T, Nakano Y, Mutoh Y, Suzuki Y, Murakami K, Okada Y, Koike R, Kitagawa Y, Kimura A, Imoto S, Miyano S, Ogawa S, Kanai T, Fukunaga K.