1: Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery.

Nature.

2019 Jan;565(7738):246-250. doi: 10.1038/s41586-018-0824-5

Ito M, Komai K, Mise-Omata S, Iizuka-Koga M, Noguchi Y, Kondo T, Sakai R, Matsuo K, Nakayama T, Yoshie O, Nakatsukasa H, Chikuma S, Shichita T, Yoshimura A.

Cerebral infarction is a major cause of death and of patients becoming bedridden, but current treatments are limited to the early stages of onset. The development of new, effective therapeutic drugs for the chronic phase, which occurs after a significant amount of time has passed since onset, is highly anticipated. Our research group has previously clarified the inflammatory process centered on macrophages during the acute phase, within a few days after the onset of cerebral infarction. On the other hand, it was previously thought that from one week after onset, the inflammation subsides and the immune system is not involved in the pathology. However, using a mouse model of cerebral infarction, our research group discovered that regulatory T cells (Tregs) accumulate and regulate the neural repair process in the brain during the chronic phase after cerebral infarction. Tregs are important cells that normally suppress inflammation and control immune responses, but it has recently become known that they also exist within tissues, contributing to tissue homeostasis and remodeling. We found that brain Tregs release a reparative factor called amphiregulin, which suppresses activated astrocytes that damage nerve cells, thereby alleviating neurological symptoms. Furthermore, it was revealed that these brain Tregs express serotonin receptors, which are characteristic of the nervous system, and are proliferated and activated by serotonin. When a type of antidepressant that increases serotonin in the brain was administered, we found that brain Tregs increased and neurological symptoms improved. It is expected that drugs and treatments that increase brain Tregs will also be useful for treating cerebral infarction patients during the chronic phase (rehabilitation period).

(Akihiko Yoshimura [equivalent to the 60th graduating class] and Minako Ito, Department of Microbiology and Immunology)

Nature Methods,

volume 16, pages255–262 (2019)

Kimberly A. Homan, Navin Gupta, Katharina T. Kroll, David B. Kolesky, Mark Skylar-Scott, Tomoya Miyoshi, Donald Mau, M. Todd Valerius, Thomas Ferrante, Joseph V. Bonventre, Jennifer A. Lewis & Ryuji Morizane

The Morizane Lab at Harvard Medical School has been vigorously researching methods for inducing the differentiation of human pluripotent stem cells into kidney cells and tissues. In 2015, we published a paper in *Nature Biotechnology* on the creation of kidney progenitor cells and kidney organoids and their application models. We demonstrated that we could efficiently induce three-dimensional nephron structures—previously considered difficult—with each segment organized in the same sequence as in vivo. However, creating kidney tissue capable of actually producing urine requires the simultaneous induction of vascular structures, which remained a major obstacle to clinical application. In our latest research, conducted jointly with the Wyss Institute at Harvard University, our lab has succeeded in generating more mature kidney organoids with vascular structures by using a 3D-printed cell culture chip to mimic the in vivo environment on a culture dish. We have demonstrated, for the first time in the world, a method for creating kidney tissue capable of producing urine. This research was published in *Nature Methods* and has been highly acclaimed. The Morizane Lab will continue to actively pursue approaches using these vascularized kidney organoids, from kidney disease research to drug discovery applications, and ultimately toward the realization of regenerative medicine.

(Ryuji Morizane [84th graduating class], Department of Medicine, Harvard Medical School)

AUTOPHAGY,

15 (2):242-258;10.1080/15548627.2018.1515530 FEB 1 2019

Tsugawa H, Mori H, Matsuzaki J, Sato A, Saito Y, Imoto M, Suematsu M, Suzuki H