Research summary
Three mechanistic immunology and DNA-damage-signaling papers anchor this set. In vivo blockade of CTLA-4 in normal mice triggered spontaneous chronic organ-specific autoimmune disease resembling human counterparts; the work showed CTLA-4 is constitutively expressed on a CD25+CD4+ subset comprising 5–10% of peripheral CD4+ T cells and that these cells suppress activation and proliferation of other T cells, including CTLA-4-deficient targets, when stimulated through the T cell receptor [1]. A second study dissected the vagus-nerve inflammatory reflex, which suppresses splenic TNF-alpha through alpha7 nicotinic acetylcholine receptors on macrophages despite the absence of acetylcholine-synthesizing enzymatic machinery in splenic nerve fibers. The authors identified an acetylcholine-producing memory-phenotype T cell population that completes the neural-to-cholinergic relay and is required for the reflex [2]. The third paper used Chk2-deficient mouse cells to map a checkpoint kinase pathway: Chk2-/- embryonic stem cells failed to maintain gamma-irradiation-induced G2 arrest, Chk2-/- thymocytes resisted DNA-damage-induced apoptosis, and Chk2-/- cells were defective for p53 stabilization and induction of p21 and other p53-dependent transcripts after gamma irradiation. Reintroducing Chk2 restored p53-dependent transcription, and Chk2 was shown to directly phosphorylate p53 on serine 20, a site known to interfere with Mdm2 binding [3]. The three studies share a common methodological backbone—gene-targeted mice combined with biochemical reconstitution—and span the regulatory T cell suppression of autoimmunity, the neural-immune circuit that constrains systemic cytokine output, and the kinase cascade that links double-strand-break sensing to p53 stabilization and cell-cycle arrest.
Recent publications
- Regulation of cancer cell metabolismDOI
- Modulation of oxidative stress as an anticancer strategyDOI
- OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesisDOI
- Induction and Activation of the Transcription Factor NFATc1 (NFAT2) Integrate RANKL Signaling in Terminal Differentiation of OsteoclastsDOI
- Negative Regulation of PKB/Akt-Dependent Cell Survival by the Tumor Suppressor PTENDOI
- Immunologic Self-Tolerance Maintained by Cd25+Cd4+Regulatory T Cells Constitutively Expressing Cytotoxic T Lymphocyte–Associated Antigen 4DOI
- Acetylcholine-Synthesizing T Cells Relay Neural Signals in a Vagus Nerve CircuitDOI
- An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acidDOI
- DNA Damage-Induced Activation of p53 by the Checkpoint Kinase Chk2DOI
- A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chainsDOI
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Email Tak W. Mak 6-12 months before your application deadline. Read several recent papers and reference specific work in your message. Use our how to email a Japanese professor guide for the proven email structure.
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External profiles
- ORCID: https://orcid.org/0000-0001-6766-861X
- OpenAlex: openalex.org
Profile compiled from public sources (Researchmap, OpenAlex, Kyoto University faculty directory). Last refreshed 2026-05. Report incorrect information.