A5103215054- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Immunodeficiency and Autoimmune Disorders
- IL-33, ST2, and ILC Pathways
- CAR-T cell therapy research
- NF-κB Signaling Pathways
- Pluripotent Stem Cells Research
- Renal and related cancers
- CRISPR and Genetic Engineering
- Immune responses and vaccinations
- Molecular Biology Techniques and Applications
- Genomics and Chromatin Dynamics
- Immune Response and Inflammation
- Peptidase Inhibition and Analysis
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Reproductive System and Pregnancy
- Eosinophilic Esophagitis
- Acute Lymphoblastic Leukemia research
RIKEN Center for Integrative Medical Sciences
2012-2023
Although Runx and Cbfβ transcription factor complexes are involved in the development of multiple hematopoietic lineages, their precise roles early mouse B lymphocyte differentiation remain elusive. In this study, we examined strains which Runx1, Runx3, or were deleted lineage progenitors by an mb1-cre transgene. Loss but not caused a developmental block during lymphopoiesis, resulting lack IgM+ cells reduced VH to DJH recombination. Expression core factors regulating cell development, such...
AIOLOS/IKZF3 is a member of the IKAROS family transcription factors. IKAROS/IKZF1 mutations have been previously associated with different forms primary immunodeficiency. Here we describe novel combined immunodeficiency due to an IKZF3 mutation in presenting T and B cell involvement, Pneumocystis jirovecii pneumonia, and/or chronic lymphocytic leukemia. Patients carrying AIOLOS p.N160S heterozygous variant displayed impaired humoral responses, abnormal development (high percentage CD21low...
Tle/Groucho proteins are transcriptional corepressors interacting with Tcf/Lef and Runx transcription factors, but their physiological roles in T cell development remain unknown. Conditional targeting of Tle1, Tle3 Tle4 revealed gene dose–dependent requirements for Tle CD8 + lineage cells. Upon ablating all three proteins, generation cells was greatly diminished, largely owing to redirection MHC-I–selected thymocytes CD4 lineage; the remaining CD8-positive showed aberrant up-regulation...
While group-2 innate lymphoid cells (ILC2s) are highly proliferative in allergic inflammation, the removal of overactivated ILC2s diseases has not been investigated. We previously showed that chronic airway allergy induces “exhausted-like” dysfunctional expressing T cell immunoreceptor with Ig and ITIM domains (TIGIT). However, physiological relevance these remains elusive. To precisely identify monitor TIGIT+ ILC2s, we generated TIGIT lineage tracer mice. Chronic stably induced which were...
The mouse Langerhans cell (LC) network is established through the differentiation of embryonic LC precursors. BMP7 and TGFβ1 initiate cellular signaling that essential for inducing preserving LCs in a quiescent state, respectively. Here we show loss Cbfβ2, one two RNA splice variants Cbfb gene, results long-term persistence precursors after their developmental arrest at transition into EpCAM+ stage. This phenotype caused by selective BMP7-mediated differentiation, whereas TGFβR intact,...
Multipotent hematopoietic progenitors must acquire thymus-homing capacity to initiate T lymphocyte development. Despite its importance, the transcriptional program underlying this process remains elusive. Cbfβ forms transcription factor complexes with Runx proteins, and here we show that Cbfβ2, encoded by an RNA splice variant of Cbfb gene, is essential for extrathymic differentiation cell progenitors. Furthermore, Cbfβ2 endows inducing expression principal receptor, Ccr9. This occurs via...
T follicular helper (Tfh) cells are essential for the development of germinal center B and high-affinity antibody-producing in humans mice. Here, we identify guanine nucleotide exchange factor (GEF) Rin-like (Rinl) as a negative regulator Tfh generation. Loss Rinl leads to an increase aging, upon vivo immunization acute LCMV Armstrong infection mice, human CD4+ cell vitro cultures. Mechanistically, adoptive transfer experiments using WT Rinl-KO naïve unraveled cell-intrinsic GEF-dependent...
Abstract Hematopoietic Stem Cells (HSC) hold the potential to self-renew and differentiate into most immune cell subsets throughout life. However, some specialized immunocytes like microglia, B-1 B cells γδ T emerge only during fetal life, they cannot be generated by adult HSC. We discovered that CBFβ isoform 2 (CBFβ2), an evolutionarily conserved component of RUNX transcription factor complex, reprograms HSC acquiring hematopoietic potential. While Cbfb2heterozygous mice normal numbers...
Abstract THEMIS functions in the cytoplasm as an adaptor molecule which dampens TCR signaling. During thymic development, sets affinity threshold for activation, enabling selection of conventional T cells response to low antigens. Although these events occur cytoplasm, possess a nuclear localization signal (NLS) and significant amount resides nucleus. To investigate importance nucleus, we deleted Themis NLS force cytoplasm. Surprisingly, cell development was impaired similar null mice,...