Hematopoietic cell-derived IL-15 supports NK cell development in scattered and clustered localization within the bone marrow

骨髄のNK細胞の分化に造血細胞が産生するIL-15が必須である --2種類の局在を示すNK細胞の新規分化モデル--. 京都大学プレスリリース. 2023-09-20.Natural killer (NK) cells are innate immune cells critical for protective immune responses against infection and cancer. Although NK cells differentiate in the bone marrow (BM) in an interleukin-15 (IL-15)-dependent manner, the cellular source of IL-15 remains elusive. Using NK cell reporter mice, we show that NK cells are localized in the BM in scattered and clustered manners. NK cell clusters overlap with monocyte and dendritic cell accumulations, whereas scattered NK cells require CXCR4 signaling. Using cell-specific IL-15-deficient mice, we show that hematopoietic cells, but not stromal cells, support NK cell development in the BM through IL-15. In particular, IL-15 produced by monocytes and dendritic cells appears to contribute to NK cell development. These results demonstrate that hematopoietic cells are the IL-15 niche for NK cell development in the BM and that BM NK cells are present in scattered and clustered compartments by different mechanisms, suggesting their distinct functions in the immune response

Induction of Isoforms of Tetrapyrrole Biosynthetic Enzymes, AtHEMA2 and AtFC1, under Stress Conditions and Their Physiological Functions in Arabidopsis12[W][OA]

In the tetrapyrrole biosynthetic pathway, isoforms of glutamyl-tRNA reductase (HEMA2) and ferrochelatase1 (FC1) are mainly expressed in nonphotosynthetic tissues. Here, using promoter-β-glucuronidase constructs, we showed that the expressions of Arabidopsis (Arabidopsis thaliana) HEMA2 (AtHEMA2) and FC1 (AtFC1) were induced in photosynthetic tissues by oxidative stresses such as wounding. Transcript levels and β-glucronidase activity were rapidly induced within 30 min, specifically in the wound area in a jasmonate-independent manner. Transcriptome analysis of wound-specific early inducible genes showed that AtHEMA2 and AtFC1 were coinduced with hemoproteins outside plastids, which are related to defense responses. Ozone fumigation or reagents generating reactive oxygen species induced the expression of both genes in photosynthetic tissues, suggesting that reactive oxygen species is involved in the induction. Since cycloheximide or puromycin induced the expression of both genes, inhibition of cytosolic protein synthesis is involved in the induction of these genes in photosynthetic tissues. The physiological functions of AtHEMA2 and AtFC1 were investigated using insertional knockout mutants of each gene. Heme contents of the roots of both mutants were about half of that of the respective wild types. In wild-type plants, heme contents were increased by ozone exposure. In both mutants, reduction of the ozone-induced increase in heme content was observed. These results suggest the existence of the tetrapyrrole biosynthetic pathway controlled by AtHEMA2 and AtFC1, which normally functions for heme biosynthesis in nonphotosynthetic tissues, but is induced in photosynthetic tissues under oxidative conditions to supply heme for defensive hemoproteins outside plastids

12-Oxo-Phytodienoic Acid Triggers Expression of a Distinct Set of Genes and Plays a Role in Wound-Induced Gene Expression in Arabidopsis

Jasmonic acid (JA) and methyl jasmonate (MeJA), collectively known as JAs, regulate diverse physiological processes in plants, including the response to wounding. Recent reports suggest that a cyclopentenone precursor of JA, 12-oxo-phytodienoic acid (OPDA), can also induce gene expression. However, little is known about the physiological significance of OPDA-dependent gene expression. We used microarray analysis of approximately 21,500 Arabidopsis (Arabidopsis thaliana) genes to compare responses to JA, MeJA, and OPDA treatment. Although many genes responded identically to both OPDA and JAs, we identified a set of genes (OPDA-specific response genes [ORGs]) that specifically responded to OPDA but not to JAs. ORGs primarily encoded signaling components, transcription factors, and stress response-related genes. One-half of the ORGs were induced by wounding. Analysis using mutants deficient in the biosynthesis of JAs revealed that OPDA functions as a signaling molecule in the wounding response. Unlike signaling via JAs, OPDA signaling was CORONATINE INSENSITIVE 1 independent. These results indicate that an OPDA signaling pathway functions independently of JA/MeJA signaling and is required for the wounding response in Arabidopsis