Quiescent Tissue Stem Cells Evade Immune Surveillance.

Stem cells are critical for the maintenance of many tissues, but whether their integrity is maintained in the face of immunity is unclear. Here we found that cycling epithelial stem cells, including Lgr5+ intestinal stem cells, as well as ovary and mammary stem cells, were eliminated by activated T cells, but quiescent stem cells in the hair follicle and muscle were resistant to T cell killing. Immune evasion was an intrinsic property of the quiescent stem cells resulting from systemic downregulation of the antigen presentation machinery, including MHC class I and TAP proteins, and is mediated by the transactivator NLRC5. This process was reversed upon stem cell entry into the cell cycle. These studies identify a link between stem cell quiescence, antigen presentation, and immune evasion. As cancer-initiating cells can derive from stem cells, these findings may help explain how the earliest cancer cells evade immune surveillance.

Targeted demethylation and activation of NLRC5 augment cancer immunogenicity through MHC class I.

Impaired expression of MHC (major histocompatibility complex) class I in cancers constitutes a major mechanism of immune evasion. It has been well documented that the low level of MHC class I is associated with poor prognosis and resistance to checkpoint blockade therapies. However, there is lmited approaches to specifically induce MHC class I to date. Here, we show an approach for robust and specific induction of MHC class I by targeting an MHC class I transactivator (CITA)/NLRC5, using a CRISPR/Cas9-based gene-specific system, designated TRED-I (Targeted reactivation and demethylation for MHC-I). The TRED-I system specifically recruits a demethylating enzyme and transcriptional activators on the NLRC5 promoter, driving increased MHC class I antigen presentation and accelerated CD8+ T cell activation. Introduction of the TRED-I system in an animal cancer model exhibited tumor-suppressive effects accompanied with increased infiltration and activation of CD8+ T cells. Moreover, this approach boosted the efficacy of checkpoint blockade therapy using anti-PD1 (programmed cell death protein) antibody. Therefore, targeting NLRC5 by this strategy provides an attractive therapeutic approach for cancer.

NLRC5/MHC class I transactivator: A key target for immune escape by SARS-CoV-2.

Antigen presentation to CD8+ T cells by MHC class I molecules is essential for host defense against viral infections. Various mechanisms have evolved in multiple viruses to escape immune surveillance and defense to support viral proliferation in host cells. Through in vitro SARS-CoV-2 infection studies and analysis of COVID-19 patient samples, we found that SARS-CoV-2 suppresses the induction of the MHC class I pathway by inhibiting the expression and function of NLRC5, a major transcriptional regulator of MHC class I genes. In this review, we discuss the molecular mechanisms for suppression of the MHC class I pathway and clinical implications for COVID-19.

FBXO11 constitutes a major negative regulator of MHC class II through ubiquitin-dependent proteasomal degradation of CIITA.

Major histocompatibility complex (MHC) class I and II molecules play critical roles in the activation and regulation of adaptive immunity through antigen presentation to CD8+ and CD4+ T cells, respectively. Strict regulation of MHC expression is critical for proper immune responses. CIITA (MHC class II transactivator), an NLR (nucleotide-binding domain, leucine-rich-repeat containing) protein, is a master regulator of MHC class II (MHC-II) gene transcription. Although it has been known that CIITA activity is regulated at the transcriptional and protein levels, the mechanism to determine CIITA protein level has not been elucidated. Here, we show that FBXO11 is a bona fide E3 ligase of CIITA and regulates CIITA protein level through ubiquitination-mediated degradation. A nonbiased proteomic approach for CIITA-binding protein identified FBXO11, a member of the Skp1-Cullin-1-F-box E3 ligase complex, as a binding partner of CIITA but not MHC class I transactivator, NLRC5. The cycloheximide chase assay showed that the half-life of CIITA is mainly regulated by FBXO11 via the ubiquitin-proteasome system. The expression of FBXO11 led to the reduced MHC-II at the promoter activity level, transcriptional level, and surface expression level through downregulation of CIITA. Moreover, human and mouse FBXO11-deficient cells display increased levels of MHC-II and related genes. In normal and cancer tissues, FBXO11 expression level is negatively correlated with MHC-II. Interestingly, the expression of FBXO11, along with CIITA, is associated with prognosis of cancer patients. Therefore, FBXO11 is a critical regulator to determine the level of MHC-II, and its expression may serve as a biomarker for cancer.

The balance between nuclear import and export of NLRC5 regulates MHC class I transactivation.

Major histocompatibility complex (MHC) class I molecules play an essential role in regulating the adaptive immune system by presenting antigens to CD8 T cells. CITA (MHC class I transactivator), also known as NLRC5 (NLR family, CARD domain-containing 5), regulates the expression of MHC class I and essential components involved in the MHC class I antigen presentation pathway. While the critical role of the nuclear distribution of NLRC5 in its transactivation activity has been known, the regulatory mechanism to determine the nuclear localization of NLRC5 remains poorly understood. In this study, a comprehensive analysis of all domains in NLRC5 revealed that the regulatory mechanisms for nuclear import and export of NLRC5 coexist and counterbalance each other. Moreover, GCN5 (general control non-repressed 5 protein), a member of HATs (histone acetyltransferases), was found to be a key player to retain NLRC5 in the nucleus, thereby contributing to the expression of MHC class I. Therefore, the balance between import and export of NLRC5 has emerged as an additional regulatory mechanism for MHC class I transactivation, which would be a potential therapeutic target for the treatment of cancer and virus-infected diseases.

The transcriptional landscape of αß T cell differentiation.

The differentiation of αßT cells from thymic precursors is a complex process essential for adaptive immunity. Here we exploited the breadth of expression data sets from the Immunological Genome Project to analyze how the differentiation of thymic precursors gives rise to mature T cell transcriptomes. We found that early T cell commitment was driven by unexpectedly gradual changes. In contrast, transit through the CD4(+)CD8(+) stage involved a global shutdown of housekeeping genes that is rare among cells of the immune system and correlated tightly with expression of the transcription factor c-Myc. Selection driven by major histocompatibility complex (MHC) molecules promoted a large-scale transcriptional reactivation. We identified distinct signatures that marked cells destined for positive selection versus apoptotic deletion. Differences in the expression of unexpectedly few genes accompanied commitment to the CD4(+) or CD8(+) lineage, a similarity that carried through to peripheral T cells and their activation, demonstrated by mass cytometry phosphoproteomics. The transcripts newly identified as encoding candidate mediators of key transitions help define the 'known unknowns' of thymocyte differentiation.

Anionic lipids facilitate membrane development and protochlorophyllide biosynthesis in etioplasts.

Dark-germinated angiosperm seedlings develop chloroplast precursors called etioplasts in cotyledon cells. Etioplasts develop lattice membrane structures called prolamellar bodies (PLBs), where the chlorophyll intermediate protochlorophyllide (Pchlide) forms a ternary complex with NADPH and light-dependent NADPH:Pchlide oxidoreductase (LPOR). The lipid bilayers of etioplast membranes are mainly composed of galactolipids, which play important roles in membrane-associated processes in etioplasts. Although etioplast membranes also contain 2 anionic lipids, phosphatidylglycerol (PG) and sulfoquinovosyldiacylglycerol (SQDG), their roles are unknown. To determine the roles of PG and SQDG in etioplast development, we characterized etiolated Arabidopsis (Arabidopsis thaliana) mutants deficient in PG and SQDG biosynthesis. A partial deficiency in PG biosynthesis loosened the lattice structure of PLBs and impaired the insertion of Mg2+ into protoporphyrin IX, leading to a substantial decrease in Pchlide content. Although a complete lack of SQDG biosynthesis did not notably affect PLB formation and Pchlide biosynthesis, lack of SQDG in addition to partial PG deficiency strongly impaired these processes. These results suggested that PG is required for PLB formation and Pchlide biosynthesis, whereas SQDG plays an auxiliary role in these processes. Notably, PG deficiency and lack of SQDG oppositely affected the dynamics of LPOR complexes after photoconversion, suggesting different involvements of PG and SQDG in LPOR complex organization. Our data demonstrate pleiotropic roles of anionic lipids in etioplast development.

Orchestration of Photosynthesis-Associated Gene Expression and Galactolipid Biosynthesis during Chloroplast Differentiation in Plants.

The chloroplast thylakoid membrane is composed of membrane lipids and photosynthetic protein complexes, and the orchestration of thylakoid lipid biosynthesis and photosynthesis-associated protein accumulation is considered important for thylakoid development. Galactolipids consist of ∼80% of the thylakoid lipids, and their biosynthesis is fundamental for chloroplast development. We previously reported that the suppression of galactolipid biosynthesis decreased the expression of photosynthesis-associated nuclear-encoded genes (PhAPGs) and photosynthesis-associated plastid-encoded genes (PhAPGs). However, the mechanism for coordinative regulation between galactolipid biosynthesis in plastids and the expression of PhANGs and PhAPGs remains largely unknown. To elucidate this mechanism, we investigated the gene expression patterns in galactolipid-deficient Arabidopsis seedlings during the de-etiolation process. We found that galactolipids are crucial for inducing both the transcript accumulation of PhANGs and PhAPGs and the accumulation of plastid-encoded photosynthesis-associated proteins in developing chloroplasts. Genetic analysis indicates the contribution of the GENOMES UNCOUPLED1 (GUN1)-mediated plastid-to-nucleus signaling pathway to PhANG regulation in response to galactolipid levels. Previous studies suggested that the accumulation of GUN1 reflects the state of protein homeostasis in plastids and alters the PhANG expression level. Thus, we propose a model that galactolipid biosynthesis determines the protein homeostasis in plastids in the initial phase of de-etiolation and optimizes GUN1-dependent signaling to regulate the PhANG expression. This mechanism might contribute to orchestrating the biosynthesis of lipids and proteins for the biogenesis of functional chloroplasts in plants.

Regulation of MHC Class I Expression in Lung Epithelial Cells during Inflammation.

Lung infections are a perennial leading cause of death worldwide. The lung epithelium comprises three main cell types: alveolar type I (AT1), alveolar type II (AT2), and bronchiolar cells. Constitutively, these three cell types express extremely low amounts of surface MHC class I (MHC I) molecules, that is, <1% of levels found on medullary thymic epithelial cells (ECs). We report that inhalation of the TLR4 ligand LPS upregulates cell surface MHC I by ∼25-fold on the three subtypes of mouse lung ECs. This upregulation is dependent on Nlrc5, Stat1, and Stat2 and caused by a concerted production of the three IFN families. It is nevertheless hampered, particularly in AT1 cells, by the limited expression of genes instrumental in the peptide loading of MHC I molecules. Genes involved in production and response to cytokines and chemokines were selectively induced in AT1 cells. However, discrete gene subsets were selectively downregulated in AT2 or bronchiolar cells following LPS inhalation. Genes downregulated in AT2 cells were linked to cell differentiation and cell proliferation, and those repressed in bronchiolar cells were primarily involved in cilium function. Our study shows a delicate balance between the expression of transcripts maintaining lung epithelium integrity and transcripts involved in Ag presentation in primary lung ECs.

Functional divergence of a pair of Arabidopsis phospho-base methyltransferases, PMT1 and PMT3, conferred by distinct N-terminal sequences.

In seed plants, phospho-base N-methyltransferase (PMT) catalyzes a key step in the biosynthesis pathway of phosphatidylcholine (PC), the most abundant phospholipid class. Arabidopsis thaliana possesses three copies of PMT, with PMT1 and PMT3 play a primary role because the pmt1 pmt3 double mutant shows considerably reduced PC content with a pale seedling phenotype. Although the function of PMT1 and PMT3 may be redundant because neither of the parental single mutants showed a similar mutant phenotype, major developmental defects and possible functional divergence of these PMTs underlying the pale pmt1 pmt3 seedling phenotype are unknown. Here, we show the major developmental defect of the pale seedlings in xylem of the hypocotyl with partial impairments in chloroplast development and photosynthetic activity in leaves. Although PMT1 and PMT3 are localized at the endoplasmic reticulum, their tissue-specific expression pattern was distinct in hypocotyls and roots. Intriguingly, the function of PMT3 but not PMT1 requires its characteristic N-terminal sequence in addition to the promoter because truncation of the N-terminal sequence of PMT3 or substitution with PMT1 driven by the PMT3 promoter failed to rescue the pale pmt1 pmt3 seedling phenotype. Thus, PMT3 function requires the N-terminal sequence in addition to its promoter, whereas the PMT1 function is defined by the promoter.

Ten-year clinical outcomes from a randomized trial comparing new-generation everolimus-eluting stent versus first-generation Sirolimus-eluting stent: Results from the RESET extended study.

BACKGROUND: New-generation drug-eluting stents (DES) achieved technological innovations and reported clinical advantages as compared with first-generation DES in clinical trials with 3-5 years follow-up. However, detailed clinical outcome data in very long-term follow-up is still scarce. OBJECTIVES: To evaluate 10-year clinical outcomes after first- and new-generation DES implantation. METHODS: In this extende follow-up study of the RESET, which is a largest randomized trial comparing everolimus-eluting stent (EES) with Sirolimus-eluting stent (SES), the study population consisted of 2892 patients from 84 centers. The primary efficacy and safety endpoints were target lesion revascularization (TLR) and a composite of death or myocardial infarction (MI), respectively. Complete 10-year follow-up was achieved in 87.9% of patients. RESULTS: Cumulative 10-year incidences of TLR and non-TLR were not significantly different between EES and SES (13.9% vs. 15.7%, Log-rank p = 0.20, and 33.4% vs. 31.3%, Log-rank p = 0.30). The cumulative 10-year incidence of death/MI was also not significantly different between the groups (32.5% vs. 34.4%, Log-rank p = 0.18). Cumulative 10-year incidence of definite stent thrombosis was numerically lower in EES than in SES (1.0% vs. 1.7%, Log-rank p = 0.16). The lower risk of EES relative to SES was significant for a composite endpoint of target lesion failure (TLF: 19.6% vs. 24.9%, Log-rank p = 0.001) and target vessel failure (TVF: 26.7% vs. 31.4%, Log-rank p = 0.006). CONCLUSION: During 10-year of follow-up, the risks for primary efficacy and safety endpoints were not significantly different between new-generation EES and first-generation SES, although EES compared with SES was associated with a lower risk for composite endpoints such as TLF and TVF.

Accuracy of ZedView, the Software for Three-Dimensional Measurement and Preoperative Planning: A Basic Study.

Background and Objectives: In the field of orthopedic surgery, novel techniques of three-dimensional shape modeling using two-dimensional tomographic images are used for bone-shape measurements, preoperative planning in joint-replacement surgery, and postoperative evaluation. ZedView® (three-dimensional measurement instrument and preoperative-planning software) had previously been developed. Our group is also using ZedView® for preoperative planning and postoperative evaluation for more accurate implant placement and osteotomy. This study aimed to evaluate the measurement error in this software in comparison to a three-dimensional measuring instrument (3DMI) using human bones. Materials and Methods: The study was conducted using three bones from cadavers: the pelvic bone, femur, and tibia. Three markers were attached to each bone. Study 1: The bones with markers were fixed on the 3DMI. For each bone, the coordinates of the center point of the markers were measured, and the distances and angles between these three points were calculated and defined as "true values." Study 2: The posterior surface of the femur was placed face down on the 3DMI, and the distances from the table to the center of each marker were measured and defined as "true values." In each study, the same bone was imaged using computed tomography, measured with this software, and the measurement error from the corresponding "true values" was calculated. Results: Study 1: The mean diameter of the same marker using the 3DMI was 23.951 ± 0.055 mm. Comparisons between measurements using the 3DMI and this software revealed that the mean error in length was <0.3 mm, and the error in angle was <0.25°. Study 2: In the bones adjusted to the retrocondylar plane with the 3DMI and this software, the average error in the distance from the planes to each marker was 0.43 (0.32-0.58) mm. Conclusion: This surgical planning software could measure the distance and angle between the centers of the markers with high accuracy; therefore, this is very useful for pre- and postoperative evaluation.

Photosynthesis and Cell Growth Trigger Degradation of Phycobilisomes during Nitrogen Limitation.

Under nitrogen (N)-limited conditions, the non-N2-fixing cyanobacterium Synechocystis sp. PCC 6803 (Synechocystis 6803) actively grows during early stages of starvation by performing photosynthesis but gradually stops the growth and eventually enters dormancy to withstand long-term N limitation. During N limitation, Synechocystis 6803 cells degrade the large light-harvesting antenna complex phycobilisomes (PBSs) presumably to avoid excess light absorption and to reallocate available N to essential functions for growth and survival. These two requirements may be driving forces for PBS degradation during N limitation, but how photosynthesis and cell growth affect PBS degradation remains unclear. To address this question, we examined involvements of photosynthesis and cell growth in PBS degradation during N limitation. Treatment of photosynthesis inhibitors and shading suppressed PBS degradation and caused non-bleaching of cells during N limitation. Limitations of photosynthesis after initial gene responses to N limitation suppressed PBS degradation, implying that photosynthesis affects PBS degradation in a post-translational manner. In addition, limitations of cell growth by inhibition of peptidoglycan and fatty acid biosynthesis, low growth temperature and phosphorous starvation suppressed PBS degradation during N limitation. Because decreased photosynthetic activity led to decreased cell growth, and vice versa, photosynthesis and cell growth would inseparably intertwine each other and affect PBS degradation during N limitation in a complex manner. Our data shed light on the coordination mechanisms among photosynthesis, cell growth and PBS degradation during N limitation.

Photosynthesis and Cell Growth Trigger Degradation of Phycobilisomes during Nitrogen Limitation.

Under nitrogen (N)-limited conditions, the non-N2-fixing cyanobacterium Synechocystis sp. PCC 6803 (Synechocystis 6803) actively grows during early stages of starvation by performing photosynthesis but gradually stops the growth and eventually enters dormancy to withstand long-term N limitation. During N limitation, Synechocystis 6803 cells degrade the large light-harvesting antenna complex phycobilisomes (PBSs) presumably to avoid excess light absorption and to reallocate available N to essential functions for growth and survival. These two requirements may be driving forces for PBS degradation during N limitation, but how photosynthesis and cell growth affect PBS degradation remains unclear. To address this question, we examined involvements of photosynthesis and cell growth in PBS degradation during N limitation. Treatment of photosynthesis inhibitors and shading suppressed PBS degradation and caused non-bleaching of cells during N limitation. Limitations of photosynthesis after initial gene responses to N limitation suppressed PBS degradation, implying that photosynthesis affects PBS degradation in a post-translational manner. In addition, limitations of cell growth by inhibition of peptidoglycan and fatty acid biosynthesis, low growth temperature and phosphorous starvation suppressed PBS degradation during N limitation. Because decreased photosynthetic activity led to decreased cell growth, and vice versa, photosynthesis and cell growth would inseparably intertwine each other and affect PBS degradation during N limitation in a complex manner. Our data shed light on the coordination mechanisms among photosynthesis, cell growth and PBS degradation during N limitation.

Identification of ANXA2 on epithelial cells as a new receptor for secretory IgA using immunoprecipitation and mass spectrometry.

Secretory immunoglobulin A plays an important role in the protection against exogenous pathogens and antigens, but it has also been reported to have pathogenic potential. We previously found that secretory immunoglobulin A accumulated in the peripheral lungs during idiopathic pulmonary fibrosis and that transferrin receptor/CD71 was partially involved in secretory immunoglobulin A-induced inflammatory cytokine production in A549 cells. This study aimed to identify the receptor responsible for the induction of cytokine production by secretory immunoglobulin A-stimulated airway epithelial cells. To this end, immunoprecipitation followed by time-of-flight mass spectrometry and peptide mass fingerprinting were performed and Annexin A2 was detected as a novel receptor for secretory immunoglobulin A. Enzyme-linked immunosorbent assay demonstrated binding of secretory immunoglobulin A to Annexin A2, and flow cytometry showed robust expression of Annexin A2 on the surface of BEAS-2B cells, A549 cells, and normal human bronchial/tracheal epithelial cells. Experiments in A549 cells using Annexin A2 small interfering RNA and neutralizing antibodies suggested that Annexin A2 was partially involved in the production of interleukin-8/CXCL8 and C-C motif chemokine ligand 2/monocyte chemoattractant protein-1 induced by secretory immunoglobulin A. Immunohistochemistry using lung sections revealed clear expression of Annexin A2 on airway epithelial cells, although the staining remained equivalent in idiopathic pulmonary fibrosis, asthma, and healthy control lungs. In conclusion, we identified that Annexin A2 expressed in airway epithelial cells is a novel receptor for secretory immunoglobulin A, which is involved in cytokine synthesis.

Lipids in photosynthetic protein complexes in the thylakoid membrane of plants, algae, and cyanobacteria.

In the thylakoid membrane of cyanobacteria and chloroplasts, many proteins involved in photosynthesis are associated with or integrated into the fluid bilayer matrix formed by four unique glycerolipid classes, monogalactosyldiacylglycerol, digalactosyldiacylglycerol, sulfoquinovosyldiacylglycerol, and phosphatidylglycerol. Biochemical and molecular genetic studies have revealed that these glycerolipids play essential roles not only in the formation of thylakoid lipid bilayers but also in the assembly and functions of photosynthetic complexes. Moreover, considerable advances in structural biology have identified a number of lipid molecules within the photosynthetic complexes such as PSI and PSII. These data have provided important insights into the association of lipids with protein subunits in photosynthetic complexes and the distribution of lipids in the thylakoid membrane. Here, we summarize recent high-resolution observations of lipid molecules in the structures of photosynthetic complexes from plants, algae, and cyanobacteria, and evaluate the distribution of lipids among photosynthetic protein complexes and thylakoid lipid bilayers. By integrating the structural information into the findings from biochemical and molecular genetic studies, we highlight the conserved and differentiated roles of lipids in the assembly and functions of photosynthetic complexes among plants, algae, and cyanobacteria.

Impacts of phosphatidylglycerol on plastid gene expression and light induction of nuclear photosynthetic genes.

Phosphatidylglycerol (PG) is the only major phospholipid in the thylakoid membrane of chloroplasts. PG is essential for photosynthesis, and loss of PG in Arabidopsis thaliana results in severe defects of growth and chloroplast development, with decreased chlorophyll accumulation, impaired thylakoid formation, and down-regulation of photosynthesis-associated genes encoded in nuclear and plastid genomes. However, how the absence of PG affects gene expression and plant growth remains unclear. To elucidate this mechanism, we investigated transcriptional profiles of a PG-deficient Arabidopsis mutant pgp1-2 under various light conditions. Microarray analysis demonstrated that reactive oxygen species (ROS)-responsive genes were up-regulated in pgp1-2. However, ROS production was not enhanced in the mutant even under strong light, indicating limited impacts of photooxidative stress on the defects of pgp1-2. Illumination to dark-adapted pgp1-2 triggered down-regulation of photosynthesis-associated nuclear-encoded genes (PhANGs), while plastid-encoded genes were constantly suppressed. Overexpression of GOLDEN2-LIKE1 (GLK1), a transcription factor gene regulating chloroplast development, in pgp1-2 up-regulated PhANGs but not plastid-encoded genes along with chlorophyll accumulation. Our data suggest a broad impact of PG biosynthesis on nuclear-encoded genes partially via GLK1 and a specific involvement of this lipid in plastid gene expression and plant development.

IFN-λ Enhances Constitutive Expression of MHC Class I Molecules on Thymic Epithelial Cells.

Regulation of MHC class I (MHC I) expression has been studied almost exclusively in hematolymphoid cells. We report that thymic epithelial cells (TECs), particularly the medullary TECs, constitutively express up to 100-fold more cell surface MHC I proteins than epithelial cells (ECs) from the skin, colon, and lung. Differential abundance of cell surface MHC I in primary ECs is regulated via transcription of MHC I and of genes implicated in the generation of MHC I-binding peptides. Superior MHC I expression in TECs is unaffected by deletion of Ifnar1 or Ifngr1, but is lessened by deletion of Aire, Ifnlr1, Stat1, or Nlrc5, and is driven mainly by type III IFN produced by medullary TECs. Ifnlr1 -/- mice show impaired negative selection of CD8 thymocytes and, at 9 mo of age, present autoimmune manifestations. Our study shows unanticipated variation in MHC I expression by ECs from various sites and provides compelling evidence that superior expression of MHC I in TECs is crucial for proper thymocyte education.

Influence of lumbosacral transitional vertebrae on spinopelvic parameters using biplanar slot scanning full body stereoradiography-analysis of 291 healthy volunteers.

BACKGROUND: Proper identification of lumbosacral transitional vertebrae (LSTV) is important to characterize the relationship between the transitional segment and adjacent levels. Classical classification schemes are inaccurate with respect to the whole spine. We propose a precise vertebral numbering method and investigated the relationship between LSTV and whole-body sagittal alignment. METHODS: A total of 291 healthy adult volunteers with no history of spinal disease were evaluated with biplanar slot scanning full body stereoradiography to determine the prevalence of LSTV. Vertebrae were counted from the first cervical vertebra using both coronal and sagittal plane images. We then investigated the influence of LSTV on whole-body sagittal alignment in 279 participants. Whole-body key parameters descriptive statistics were compared among groups according to the number of vertebrae (L4, L5, and L6). Statistical analysis was performed between normal and LSTV cases using the Steel-Dwass analysis. RESULTS: Of the 291 subjects, 14 (4.8%) had 23 vertebrae and 16 (5.5%) had 25 vertebrae. Eleven (3.8%) had Th11, 3 (1.0%) had L4, and 1 (0.3%) had Th11 + L6, 16 (5.5%) had L6. Compared with the normal group, the sacral base in relation to the pelvis was higher in the L4 group and lower in the L6 group. The C2-C7 angle and lumbar lordosis (LL) were increased in both the L4 and L6 groups. All remaining parameters were decreased in the L4 group and increased in the L6 group. The relationship between LL and PI was similar in the normal and LSTV groups, despite the difference in the sacral base location. CONCLUSIONS: We propose a precise method for numbering the vertebrae using coronal and sagittal full body images. The spinopelvic parameters of the LSTV population significantly differed from those in the normal spine population due to differences in the sacral base location.

MHC class I transactivator NLRC5 in host immunity, cancer and beyond.

The presentation of antigenic peptides by major histocompatibility complex (MHC) class I and class II molecules is crucial for activation of the adaptive immune system. The nucleotide-binding domain and leucine-rich repeat receptor family members CIITA and NLRC5 function as the major transcriptional activators of MHC class II and class I gene expression, respectively. Since the identification of NLRC5 as the master regulator of MHC class I and class-I-related genes, there have been major advances in understanding the function of NLRC5 in infectious diseases and cancer. Here, we discuss the biological significance and mechanism of NLRC5-dependent MHC class I expression.