Akihiko Yoshimura
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View article: Germline variants and mosaic chromosomal alterations affect COVID-19 vaccine immunogenicity
Germline variants and mosaic chromosomal alterations affect COVID-19 vaccine immunogenicity Open
Vaccine immunogenicity is influenced by the vaccinee's genetic background. Here, we perform a genome-wide association study of vaccine-induced SARS-CoV-2-specific immunoglobulin G (IgG) antibody titers and T cell immune responses in 1,559 …
View article: SHIP-1 regulates the differentiation and function of Tregs via inhibiting mTORC1 activity
SHIP-1 regulates the differentiation and function of Tregs via inhibiting mTORC1 activity Open
Cell metabolism is crucial for orchestrating the differentiation and function of regulatory T cells (Tregs). However, the underlying mechanism that coordinates cell metabolism to regulate Treg activity is not completely understood. As a pi…
View article: The Nr4a family regulates intrahepatic Treg proliferation and liver fibrosis in MASLD models
The Nr4a family regulates intrahepatic Treg proliferation and liver fibrosis in MASLD models Open
Metabolic dysfunction-associated steatotic hepatitis (MASH) is a chronic progressive liver disease that is highly prevalent worldwide. MASH is characterized by hepatic steatosis, inflammation, fibrosis, and liver damage, which eventually r…
View article: Gelsolin alleviates rheumatoid arthritis by negatively regulating NLRP3 inflammasome activation
Gelsolin alleviates rheumatoid arthritis by negatively regulating NLRP3 inflammasome activation Open
Despite numerous biomarkers being proposed for rheumatoid arthritis (RA), a gap remains in our understanding of their mechanisms of action. In this study, we discovered a novel role for gelsolin (GSN), an actin-binding protein whose levels…
View article: NR4A ablation improves mitochondrial fitness for long persistence in human CAR-T cells against solid tumors
NR4A ablation improves mitochondrial fitness for long persistence in human CAR-T cells against solid tumors Open
Background Antitumor effect of chimeric antigen receptor (CAR)-T cells against solid tumors is limited due to various factors, such as low infiltration rate, poor expansion capacity, and exhaustion of T cells within the tumor. NR4A transcr…
View article: Effect of nonsense-mediated mRNA decay factor SMG9 deficiency on premature aging in zebrafish
Effect of nonsense-mediated mRNA decay factor SMG9 deficiency on premature aging in zebrafish Open
SMG9 is an essential component of the nonsense-mediated mRNA decay (NMD) machinery, a quality control mechanism that selectively degrades aberrant transcripts. Mutations in SMG9 are associated with heart and brain malformation syndrome (HB…
View article: Multi-omics study reveals different pathogenesis of the generation of skin lesions in SLE and IDLE patients
Multi-omics study reveals different pathogenesis of the generation of skin lesions in SLE and IDLE patients Open
Lupus erythematosus (LE) is a heterogeneous, antibody-mediated autoimmune disease. Isolate discoid LE (IDLE) and systematic LE (SLE) are traditionally regarded as the two ends of the spectrum, ranging from skin-limited damage to life-threa…
View article: DHCR7 links cholesterol synthesis with neuronal development and axonal integrity
DHCR7 links cholesterol synthesis with neuronal development and axonal integrity Open
The DHCR7 enzyme converts 7-DHC into cholesterol. Mutations in DHCR7 can block cholesterol production, leading to abnormal accumulation of 7-DHC and causing Smith-Lemli-Opitz syndrome (SLOS). SLOS is an autosomal recessive disorder charact…
View article: Disruption of post-thymic tolerance in skin-reactive TCR transgenic mice through the interaction of lymphopenia and intestinal microbiota
Disruption of post-thymic tolerance in skin-reactive TCR transgenic mice through the interaction of lymphopenia and intestinal microbiota Open
Autoimmune diseases often arise from conditions where the immune system is compromised. While lymphopenia-induced proliferation (LIP) is crucial for immune system development and maturation, it is also caused by environmental insults, such…
View article: NR4a1/2 deletion promotes accumulation of TCF1+ stem-like precursors of exhausted CD8+ T cells in the tumor microenvironment
NR4a1/2 deletion promotes accumulation of TCF1+ stem-like precursors of exhausted CD8+ T cells in the tumor microenvironment Open
T cell exhaustion impairs tumor immunity and contributes to resistance against immune checkpoint inhibitors. The nuclear receptor subfamily 4 group A (NR4a) family of nuclear receptors plays a crucial role in driving T cell exhaustion. In …
View article: NR4A3 deficiency ameliorates contact hypersensitivity and exacerbates psoriasis by regulating gene expression in dendritic cells
NR4A3 deficiency ameliorates contact hypersensitivity and exacerbates psoriasis by regulating gene expression in dendritic cells Open
NR4A3 is a transcription factor that belongs to the nuclear receptor superfamily. To reveal the roles of NR4A3 in skin diseases, we constructed contact hypersensitivity (CHS)- and imiquimod-induced psoriasis models in Nr4a3 -/- mice. In th…
View article: Enhancing Anti-Tumor Activity of CAR T CellsThrough FOXO1-Mediated Stemness and Mitochondrial Fitness
Enhancing Anti-Tumor Activity of CAR T CellsThrough FOXO1-Mediated Stemness and Mitochondrial Fitness Open
Loss of stemness and mitochondrial dysfunction induced by chronic antigen stimulation represents formidable obstacles in chimeric antigen receptor (CAR) T cell therapy for solid tumors. However, the regulation of stemness and mitochondrial…
View article: Immune Cell Senescence and body Aging
Immune Cell Senescence and body Aging Open
Immune system aging (immune senescence) is an important factor contributing to the increased incidence and mortality rates among the elderly. Immune senescence, characterized by a decline in immune function, can also lead to aging and tiss…
View article: Hepatic stellate cell-intrinsic role of SOCS1 in controlling hepatic fibrogenic response and the pro-inflammatory macrophage compartment during liver fibrosis
Hepatic stellate cell-intrinsic role of SOCS1 in controlling hepatic fibrogenic response and the pro-inflammatory macrophage compartment during liver fibrosis Open
Introduction Hepatic stellate cells (HSC) become activated, differentiate to myofibroblasts and produce extracellular fibrillar matrix during liver fibrosis. The hepatic fibrogenic response is orchestrated by reciprocal interactions betwee…
View article: The gut microbiota-induced kynurenic acid recruits GPR35-positive macrophages to promote experimental encephalitis
The gut microbiota-induced kynurenic acid recruits GPR35-positive macrophages to promote experimental encephalitis Open
The intricate interplay between gut microbes and the onset of experimental autoimmune encephalomyelitis (EAE) remains poorly understood. Here, we uncover remarkable similarities between CD4+ T cells in the spinal cord and their counterpart…
View article: SOCS3 deletion in effector T cells confers an anti-tumorigenic role of IL-6 to the pro-tumorigenic cytokine
SOCS3 deletion in effector T cells confers an anti-tumorigenic role of IL-6 to the pro-tumorigenic cytokine Open
Interleukin (IL)-6 is abundantly expressed in the tumor microenvironment and is associated with poor patient outcomes. Here, we demonstrate that the deletion of the suppressor of cytokine signaling 3 (SOCS3) in T cells potentiates anti-tum…
View article: Cellular and Humoral Immune Responses after Breakthrough Infection in Patients Undergoing Hemodialysis
Cellular and Humoral Immune Responses after Breakthrough Infection in Patients Undergoing Hemodialysis Open
Coronavirus disease 2019 (COVID-19) following primary immunization (breakthrough infection) has been reported in hemodialysis patients; however, their post-infection immune status remains unclear. We evaluated the humoral and cellular immu…
View article: FigureS5 from Inhibition of Nr4a Receptors Enhances Antitumor Immunity by Breaking Treg-Mediated Immune Tolerance
FigureS5 from Inhibition of Nr4a Receptors Enhances Antitumor Immunity by Breaking Treg-Mediated Immune Tolerance Open
Validation of the chemotherapeutic agent Camptothecin as a functional Nr4a inhibitor
View article: FigureS7 from Inhibition of Nr4a Receptors Enhances Antitumor Immunity by Breaking Treg-Mediated Immune Tolerance
FigureS7 from Inhibition of Nr4a Receptors Enhances Antitumor Immunity by Breaking Treg-Mediated Immune Tolerance Open
Camptothecin and a COX-2 inhibitor regulate Treg-mediated down-regulation of costimulatory molecules on tumor-infiltrating DCs
View article: Supplementary Data from Inhibition of Nr4a Receptors Enhances Antitumor Immunity by Breaking Treg-Mediated Immune Tolerance
Supplementary Data from Inhibition of Nr4a Receptors Enhances Antitumor Immunity by Breaking Treg-Mediated Immune Tolerance Open
Supplementary methods and legends
View article: FigureS2 from Inhibition of Nr4a Receptors Enhances Antitumor Immunity by Breaking Treg-Mediated Immune Tolerance
FigureS2 from Inhibition of Nr4a Receptors Enhances Antitumor Immunity by Breaking Treg-Mediated Immune Tolerance Open
Treg-specific deletion of Nr4a1 and Nr4a2 attenuated Treg cell suppressive activities
View article: FigureS1 from Inhibition of Nr4a Receptors Enhances Antitumor Immunity by Breaking Treg-Mediated Immune Tolerance
FigureS1 from Inhibition of Nr4a Receptors Enhances Antitumor Immunity by Breaking Treg-Mediated Immune Tolerance Open
Expression of Nr4a factors in human Treg cells
View article: FigureS3 from Inhibition of Nr4a Receptors Enhances Antitumor Immunity by Breaking Treg-Mediated Immune Tolerance
FigureS3 from Inhibition of Nr4a Receptors Enhances Antitumor Immunity by Breaking Treg-Mediated Immune Tolerance Open
Potent anti-tumor immune responses were induced in Nr4a-DcKO mice
View article: Data from Inhibition of Nr4a Receptors Enhances Antitumor Immunity by Breaking Treg-Mediated Immune Tolerance
Data from Inhibition of Nr4a Receptors Enhances Antitumor Immunity by Breaking Treg-Mediated Immune Tolerance Open
Enhanced infiltration of regulatory T cells (Treg) into tumor tissue is detrimental to patients with cancer and is closely associated with poor prognosis as they create an immunosuppressive state that suppresses antitumor immune responses.…
View article: FigureS6 from Inhibition of Nr4a Receptors Enhances Antitumor Immunity by Breaking Treg-Mediated Immune Tolerance
FigureS6 from Inhibition of Nr4a Receptors Enhances Antitumor Immunity by Breaking Treg-Mediated Immune Tolerance Open
Camptothecin and a COX-2 inhibitor induced anti-tumor effects in a MC38 tumor model