Treatment with DHA/EPA ameliorates atopic dermatitis-like skin disease by blocking LTB4 production

Atopic dermatitis (AD) is caused by both dysregulated immune responses and an impaired skin barrier. Although leukotriene B4 (LTB4) is involved in tissue inflammation that occurs in several disorders, including AD, therapeutic strategies based on LTB4 inhibition have not been explored. Here we demonstrate that progression of an AD-like skin disease in NC/Nga mice is inhibited when docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) is administered together with FK506. Treatment with DHA/EPA and FK506 decreases the clinical score of dermatitis in NC/Nga mice and lowers local LTB4 concentrations. The treatment also suppressed the infiltration of T cells, B cells, eosinophils and neutrophils, and promoted reduced serum IgE levels. Secretion of IL-13 and IL-17A in CD4+ T cells was lower in DHA/EPA- and FK506-treated mice than in mice treated with FK506 alone. The inhibition of disease progression induced by DHA/EPA was reversed by local injection of LTB4, suggesting that the therapeutic effect of DHA/EPA is LTB4-dependent. Our results demonstrate that treatment of AD with DHA/EPA is effective for allergic skin inflammation and acts by suppressing LTB4 production

Expression dynamics of HAND1/2 in in vitro human cardiomyocyte differentiation

転写因子HAND1とHAND2の発現パターンと役割の解明 --ヒトiPS細胞から増殖能の高い心筋細胞を回収する--. 京都大学プレスリリース. 2021-07-27.Three genes determine heart cell growth. 京都大学プレスリリース. 2021-07-27.Hand1 and Hand2 are transcriptional factors, and knockout mice of these genes show left and right ventricular hypoplasia, respectively. However, their function and expression in human cardiogenesis are not well studied. To delineate their expressions and assess their functions in human cardiomyocytes (CMs) in vitro, we established two triple-reporter human induced pluripotent stem cell lines that express HAND1[mCherry], HAND2[EGFP] and either MYH6-driven iRFP670 or tagBFP constitutively and investigated their expression dynamics during cardiac differentiation. On day 5 of the differentiation, HAND1 expression marked cardiac progenitor cells. We profiled the CM subpopulations on day 20 with RNA sequencing and found that mCherry+ CMs showed higher proliferative ability than mCherry− CMs and identified a gene network of LEF1, HAND1, and HAND2 to regulate proliferation in CMs. Finally, we identified CD105 as a surface marker of highly proliferative CMs