1:RUNX-CBFβ-driven enhancer directs the Irf8 dose-dependent lineage choice between DCs and monocytes.

Nat Immunol.

2021 Mar;22(3):301-311. doi: 10.1038/s41590-021-00871-y.

Murakami K, Sasaki H, Nishiyama A, Kurotaki D, Kawase W, Ban T, Nakabayashi J, Kanzaki S, Sekita Y, Nakajima H, Ozato K, Kimura T, Tamura T.

Monocytes and dendritic cells differentiate from a common progenitor cell, and the transcription factor Interferon regulatory factor 8 (IRF8) is crucial for this fate determination. However, the mechanism by which IRF8 controls differentiation was unknown. Through detailed epigenomic analysis, the authors identified a novel enhancer important for regulating the expression of the Irf8 gene. By analyzing mice lacking this region, they revealed that multiple enhancers, including this one, control the expression of the Irf8 gene. Furthermore, they found that this region is controlled by the transcription factor RUNX-CBFb and that differences in IRF8 expression levels determine the differentiation fate of myeloid cells. The first author, Koichi Murakami (Department of Hematology, Class of '90), began his research in my laboratory five years ago. After publishing a study on the functional regulation of hematopoietic stem cells (see Other Published Papers) in *Cell Reports*, he has now achieved the remarkable feat of publishing this immunology study in *Nature Immunology*. I look forward to his future developments.

(Hideaki Nakajima, Class of '66, Department of Hematology, Immunology and Infectious Diseases, Yokohama City University School of Medicine)

Science Advances

03 Mar 2021:　Vol. 7, no. 10, eabd6480, DOI: 10.1126/sciadv.abd6480

M Suzuki, T Sujino, S Chiba, Y Harada, M Goto, R Takahashi, M Mita, K Hamase, T Kanai, M Ito, M K Waldor, M Yasui, J Sasabe

Many amino acids have chirality and exist as optical isomers (D- and L-forms). Unlike other organisms that selectively use L-amino acids, eubacteria convert various L-amino acids to their D-forms and use them as materials for their cell walls. However, the role of D-amino acids, which can be considered metabolites characteristic of eubacteria, in mammalian immunity remained unclear. This study revealed that an enzyme expressed in the mammalian gut specifically recognizes and metabolizes D-amino acids derived from symbiotic bacteria, thereby influencing the fate of intestinal B lymphocytes and regulating the production of immunoglobulin A. This immunomodulation by amino acid chirality is thought to help maintain the symbiotic relationship with eubacteria, and it is expected to become a new therapeutic target for diseases caused by its disruption. Furthermore, it will help elucidate the evolutionary significance of chiral selection of amino acids by life in the competition for survival.

(Masato Yasui, Class of '68; Junpei Sasabe, Class of '81; Department of Pharmacology)

Redox Biology.

2021 Feb 28; 41:101921. doi: 10.1016/j.redox.2021.101921.

Kohei Homma, Eriko Toda, Hideto Osada, Norihiro Nagai, Takumi Era, Kazuo Tsubota, Hideyuki Okano, Yoko Ozawa*

Cell Rep.

2021 Jan 5;34(1):108579. doi: 10.1016/j.celrep.2020.108579.

Murakami K, Kurotaki D, Kawase W, Soma S, Fukuchi Y, Kunimoto H, Yoshimi R, Koide S, Oshima M, Hishiki T, Hayakawa N, Matsuura T, Oda M, Yanagisawa K, Kobayashi H, Haraguchi M, Atobe Y, Funakoshi K, Iwama A, Takubo K, Okamoto S, Tamura T, Nakajima H.