1: CD8+ tissue-resident memory T cells promote liver fibrosis resolution by inducing apoptosis of hepatic stellate cells.

Nat Commun

12(1): 4474, 2021 doi: 10.1038/s41467-021-24734-0

Koda Y, Teratani T, Chu PS, Hagihara Y, Mikami Y, Harada Y, Tsujikawa H, Miyamoto K, Suzuki T, Taniki N,Sujino T, Sakamoto M, Kanai T, Nakamoto N.

Nonalcoholic steatohepatitis (NASH) presents with liver inflammation and hepatocyte ballooning and carries the risk of progressing to cirrhosis and liver cancer, but no effective medical treatment currently exists. Traditionally, liver fibrosis was considered irreversible, but this established theory is being overturned by reports of cases where liver fibrosis improved after the hepatitis virus was eliminated with therapeutic drugs. In a joint study with the Department of Pathology, we reproduced the process of NASH pathology in mice—from onset and progression to recovery through dietary therapy—and discovered that during the recovery phase, "tissue-resident memory CD8 T cells (CD8 Trm)" are involved in the resolution of liver fibrosis. Furthermore, we clarified that CD8 Trm cells promote recovery from fibrosis by inducing apoptosis in hepatic stellate cells, the main culprits in fibrosis, via the Fas ligand (Figure 1). These cells have also been confirmed in the liver tissue of NASH patients, and it is hoped that the results of this research will lead to the development of future treatments and diagnostic agents for fibrotic diseases of the liver and other organs.

(Nobuhiro Nakamoto, Class of '77, Department of Gastroenterology and Hepatology)

J Am Coll Cardiol

2021 Aug 24;78(8):763-777.

Shoji S, Kuno T, Fujisaki T, Takagi H, Briasoulis A, Deharo P, Cuisset T, Latib A, Kohsaka S.

After treatment for acute coronary syndromes, "dual antiplatelet therapy" (aspirin and a P2Y12 inhibitor) is required. Regarding P2Y12 inhibitors, new-generation drugs with more potent effects have recently been developed, and their use is becoming a global trend. However, potent antiplatelet drugs also increase the risk of bleeding, which has been a major issue, particularly in Japan (Shoji et al., JAMA Netw Open 2020). The strategy of "de-escalation" of antiplatelet therapy was therefore proposed. Unfortunately, however, the randomized controlled trials (RCTs) conducted on this strategy have been small, and it has been difficult to make firm recommendations regarding "de-escalation." Therefore, Shoji, Kuno, and Kohsaka aggregated data from 15 trials and conducted a network meta-analysis to investigate the merits of this strategy. The results exceeded previous expectations, suggesting that the de-escalation strategy not only prevents bleeding complications but also helps prevent the recurrence of thrombotic complications (Figure). This work, originating from Asia, is expected to significantly contribute to future clinical practice guideline recommendations worldwide.

(Keiichi Fukuda, Class of '62, Department of Cardiology)

Nat Commun.

2021 Aug 26;12(1):5146. doi: 10.1038/s41467-021-25488-5.

Yoshihiko Yamazaki, Yoshifumi Abe, Satoshi Fujii, Kenji F Tanaka

Mol Psychiatry.

2021 Sep 28. doi: 10.1038/s41380-021-01297-6. Epub ahead of print. PMID: 34584230.

Nakahara T, Tsugawa S, Noda Y, Ueno F, Honda S, Kinjo M, Segawa H, Hondo N, Mori Y, Watanabe H, Nakahara K, Yoshida K, Wada M, Tarumi R, Iwata Y, Plitman E, Moriguchi S, de la Fuente-Sandoval C, Uchida H, Mimura M.

EMBO J.

2021 Sep 15;40(18):e108345. doi: 10.15252

Iwasaki YW, Sriswasdi S, Kinugasa Y, Adachi J, Horikoshi Y, Shibuya A, Iwasaki W, Tashiro S, Tomonaga T, Siomi H.

Molecular Aspects of Medicine.

2021 Aug;80:100984. doi: 10.1016

Kinouchi K, Mikami Y, Kanai T, Itoh H.