Issues

Professor Kazuyo Moro, D.D.S., PhD, finished her doctorate in the Department of Microbiology and Immunology at Keio University School of Medicine in 2007 and then worked there as a postdoctoral fellow for 5 years. She transferred to RIKEN Center for Integrative Medical Sciences (IMS) in 2012. For the first 2 years, she worked in the Laboratory for Immune Cell Systems as a senior researcher, and in 2015, she became team leader for the Laboratory for Innate Immune Systems. Since 2019, Prof. Moro holds dual appointments at RIKEN IMS and at Osaka University Graduate School of Medicine.

Systemic sclerosis (SSc) is a debilitating autoimmune disease that preferentially afflicts women. The molecular origins of this female bias are unclear. A new study of plasmacytoid dendritic cells from SSc patients by Du et al. suggests the X chromosome may play a key role.

Sparano et al. show that tissue-resident NK cells produce TGF-β1 themselves to establish and maintain residency in glandular tissues. In these environments, TGF-β1, IL-15, and other factors collaboratively induce a Hobit-dependent cytotoxicity program. In the salivary glands, trNK cells limit murine cytomegalovirus persistence.

Bernaleau et al. show that CCDC134 located in the ER is required for TLR biogenesis by controlling the N-glycosylation, folding, and stabilization of the ER chaperone Gp96.

The authors highlight the often overlooked significance of lymphatic vessels (LVs) in cancer, revealing their active role in shaping the tumor microenvironment, influencing tumor progression, metastasis, and the immune response, challenging the traditional view of LVs as mere pathways for metastasis.

The authors describe that TLR7 and TLR8 escape X-chromosome inactivation in plasmacytoid DCs of patients with systemic sclerosis, which is associated with decreased expression of components of the XCI machinery and increased presence of pDC subclusters with high IFN-I signature.

The authors describe the mechanism by which increased stiffness in the skin regulates the activation of pDCs, and how this process is dysregulated in patients with systemic sclerosis due to the presence of inflammatory mediators such as nucleic acid-binding chemokines.

Mice lacking RNase T2 display an inflammatory phenotype in vivo in a TLR13-dependent manner, which is also observed under germ-free conditions. This suggests that RNase T2 plays an important role in limiting self-RNA recognition by preventing erroneous activation of TLR13.

Sato et al. report that the lack of RNase T2 activates TLR13, the sensor of bacterial 23S ribosomal RNAs, leading to the accumulation of tissue-protective Kupffer cells. Consequently, Rnaset2^−/− mice are resistant against acute liver injury caused by acetaminophen.

A loss-of-function genetic screen identifies the ER-resident protein CCDC134 as an essential regulator of Toll-like receptor (TLR) responses. CCDC134 binds and stabilizes the TLR chaperone Gp96, controlling thereby the folding and trafficking of the plasma membrane and endolysosomal TLRs.

Sparano et al. show that tissue-resident NK cells produce TGF-β1 themselves to establish and maintain residency in glandular tissues. In these environments, TGF-β1, IL-15, and other factors collaboratively induce a Hobit-dependent cytotoxicity program. In the salivary glands, trNK cells limit murine cytomegalovirus persistence.

Activation of CD8⁺ T cells necessitates rapid metabolic reprogramming to fulfill the substantial biosynthetic demands. This article highlights the tRNA m¹A modification as a metabolic checkpoint of cholesterol biosynthesis to enhance the tumor-killing capacity of CD8⁺ T cells, suggesting potential novel strategies for cancer immunotherapy.

This study identifies the PTPN23-PI3KC2α-AKT2 signaling axis as a critical pathway in BRAF-mutant cancers. Pharmacological targeting of this axis selectively kills BRAF-mutant tumor cells, offering a promising therapeutic strategy for treating BRAF-mutant cancers.

Chen et al. report that DEK accumulates in Fancd2^−/− HSCs and CD34⁺ cells from patients with Fanconi anemia, causing chromatin relaxation failure under replication stress. Inhibition of DEK promotes function recovery of Fancd2^−/− HSCs, suggesting DEK as a potential target.