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DAP12, an immunoreceptor tyrosine-based activation motif-bearing adapter protein, is involved in innate immunity mediated by natural killer cells and myeloid cells. We show that DAP12-deficient mouse B cells and B cells from a patient with Nasu-Hakola disease, a recessive genetic disorder resulting from loss of DAP12, showed enhanced proliferation after stimulation with anti-IgM or CpG. Myeloid-associated immunoglobulin-like receptor (MAIR) II (Cd300d) is a DAP12-associated immune receptor. Like DAP12-deficient B cells, MAIR-II-deficient B cells were hyperresponsive. Expression of a chimeric receptor composed of the MAIR-II extracellular domain directly coupled to DAP12 into the DAP12-deficient or MAIR-II-deficient B cells suppressed B cell receptor (BCR)-mediated proliferation. The chimeric MAIR-II-DAP12 receptor recruited the SH2 domain-containing protein tyrosine phosphatase 1 (SHP-1) after BCR stimulation. DAP12-deficient mice showed elevated serum antibodies against self-antigens and enhanced humoral immune responses against T cell-dependent and T cell-independent antigens. Thus, DAP12-coupled MAIR-II negatively regulates B cell-mediated adaptive immune responses.

The activating natural killer (NK) cell receptor Ly49H recognizes the mouse cytomegalovirus (MCMV) m157 glycoprotein expressed on the surface of infected cells and is required for protection against MCMV. Although Ly49H has previously been shown to signal via DAP12, we now show that Ly49H must also associate with and signal via DAP10 for optimal function. In the absence of DAP12, DAP10 enables Ly49H-mediated killing of m157-bearing target cells, proliferation in response to MCMV infection, and partial protection against MCMV. DAP10-deficient Ly49H(+) NK cells, expressing only Ly49H-DAP12 receptor complexes, are partially impaired in their ability to proliferate during MCMV infection, display diminished ERK1/2 activation, produce less IFN-gamma upon Ly49H engagement, and demonstrate reduced control of MCMV infection. Deletion of both DAP10 and DAP12 completely abrogates Ly49H surface expression and control of MCMV infection. Thus, optimal NK cell-mediated immunity to MCMV depends on Ly49H signaling through both DAP10 and DAP12.

Tillering, also known as shoot branching, is a fundamental trait for cereal crops such as rice to produce sufficient panicle numbers. Effective tillering that guarantees successful panicle production is essential for achieving high crop yields. Recent advances in molecular biology have revealed the mechanisms underlying rice tillering; however, in rice breeding and cultivation, there remain limited genes or alleles suitable for effective tillering and high yields. A recently identified quantitative trait locus (QTL) called MORE PANICLES 3 (MP3) has been cloned as a single gene and shown to promote tillering and to moderately increase panicle number. This gene is an ortholog of the maize domestication gene TB1 , and it has the potential to increase grain yield under ongoing climate change and in nutrient-poor environments. This review reconsiders the potential and importance of tillering for sustainable food production. Thus, I provide an overview of rice tiller development and the currently understood molecular mechanisms that underly it, focusing primarily on the biosynthesis and signaling of strigolactones, effective QTLs, and the importance of MP3 (TB1). The possible future benefits in using promising QTLs such as MP3 to explore agronomic solutions under ongoing climate change and in nutrient-poor environments are also highlighted. [ABSTRACT FROM AUTHOR]

Background: Leukocyte immunoglobulin‐like receptor subfamily B member 4 (LILRB4/ILT3) is an up‐and‐coming molecule that promotes immune evasion. We have previously reported that LILRB4 facilitates myeloid‐derived suppressor cells (MDSCs)‐mediated tumor metastasis in mice. This study aimed to investigate the impact of the LILRB4 expression levels on tumor‐infiltrating cells on the prognosis of non‐small cell lung cancer (NSCLC) patients. Methods: We immunohistochemically evaluated the LILRB4 expression levels of completely resected 239 NSCLC specimens. Whether the blocking of LILRB4 on human PBMC‐derived CD33+ MDSCs inhibited the migration ability of lung cancer cells was also examined using transwell migration assay. Results: The LILRB4 high group, in which patients with a high LILRB4 expression level on tumor‐infiltrating cells, showed a shorter overall survival (OS) (p = 0.013) and relapse‐free survival (RFS) (p = 0.0017) compared to the LILRB4 low group. Multivariate analyses revealed that a high LILRB4 expression was an independent factor for postoperative recurrence, poor OS and RFS. Even in the cohort background aligned by propensity score matching, OS (p = 0.023) and RFS (p = 0.0046) in the LILRB4 high group were shorter than in the LILRB4 low group. Some of the LILRB4 positive cells were positive for MDSC markers, CD33 and CD14. Transwell migration assay demonstrated that blocking LILRB4 significantly inhibited the migration of human lung cancer cells cocultured with CD33+ MDSCs. Conclusion: Together, signals through LILRB4 on tumor‐infiltrating cells, including MDSCs, play an essential role in promoting tumor evasion and cancer progression, impacting the recurrence and poor prognosis of patients with resected NSCLC. [ABSTRACT FROM AUTHOR]

SUMMARY: Improving crop yield potential through an enhanced response to rising atmospheric CO2 levels is an effective strategy for sustainable crop production in the face of climate change. Large‐sized panicles (containing many spikelets per panicle) have been a recent ideal plant architecture (IPA) for high‐yield rice breeding. However, few breeding programs have proposed an IPA under the projected climate change. Here, we demonstrate through the cloning of the rice (Oryza sativa) quantitative trait locus for MORE PANICLES 3 (MP3) that the improvement in panicle number increases grain yield at elevated atmospheric CO2 levels. MP3 is a natural allele of OsTB1/FC1, previously reported as a negative regulator of tiller bud outgrowth. The temperate japonica allele advanced the developmental process in axillary buds, moderately promoted tillering, and increased the panicle number without negative effects on the panicle size or culm thickness in a high‐yielding indica cultivar with large‐sized panicles. The MP3 allele, containing three exonic polymorphisms, was observed in most accessions in the temperate japonica subgroups but was rarely observed in the indica subgroup. No selective sweep at MP3 in either the temperate japonica or indica subgroups suggested that MP3 has not been involved and utilized in artificial selection during domestication or breeding. A free‐air CO2 enrichment experiment revealed a clear increase of grain yield associated with the temperate japonica allele at elevated atmospheric CO2 levels. Our findings show that the moderately increased panicle number combined with large‐sized panicles using MP3 could be a novel IPA and contribute to an increase in rice production under climate change with rising atmospheric CO2 levels. Significance Statement: Genetic enhancement of crop responses to the rising atmospheric CO2 levels is one way to improve crop productivity under the projected climate change. We demonstrate that a cloned rice (Oryza sativa) quantitative trait locus, MP3, promoted tillering, moderately increased the panicle number without negative effects on the panicle size or culm thickness, and clearly increased the grain yield under elevated atmospheric CO2 conditions, indicating the value for designing a novel high‐yielding ideotype under the projected climate change. [ABSTRACT FROM AUTHOR]

Dysregulation of osteoclasts, the multinucleated cells responsible for bone resorption, contributes to several degenerative bone disorders. Previously, we showed that blocking the leukocyte immunoglobulin (Ig)-like receptor B4 (LILRB4), a kind of inhibitory receptor that plays an important role in immune regulation, promotes osteoclast differentiation in vitro. Here, we explored whether gp49B, the murine ortholog of LILRB4, regulates osteoclastogenesis in vivo, and whether fibronectin (FN), a ligand of LILRB4/gp49B, certainly contributes to LILRB4/gp49B-mediated osteoclastogenesis. In comparison with wild-type mice, gp49B deficiency mice exhibited a loss of trabecular bone number and an increase in osteoclast formation. Gp49B knockout improved the bone resorptive capacity of osteoclasts derived from murine Raw264.7 cells by increasing osteoclast formation. We further revealed that gp49B deficiency increased the receptor activator of nuclear factor (NF)-κB ligand (RANKL)-induced signaling transduction by increasing the phosphorylation of transforming growth factor (TGF)-activated kinase 1 (TAK1), NF-κB and mitogen-activated protein kinases (MAPKs). Furthermore, the N-terminal 30 kDa proteolytic fragments of FN promoted gp49B-mediated inhibition of osteoclastogenesis by increasing Src homology-2-containing tyrosine phosphatase 1 (SHP-1) phosphorylation and tumor necrosis factor receptor-associated factor 6 (TRAF6)-SHP-1 association. In summary, the FN-LILRB4/gp49B interaction negatively regulates RANKL-induced TRAF6/TAK1/NF-κB/MAPK signaling in osteoclastogenesis. [ABSTRACT FROM AUTHOR]