Yukiko Baba

Publications (5)21.88 Total impact

• Article: PI3K-Akt-mTORC1-S6K1/2 axis controls Th17 differentiation by regulating Gfi1 expression and nuclear translocation of RORγ.

  Yutaka Kurebayashi, Shigenori Nagai, Ai Ikejiri, Masashi Ohtani, Kenji Ichiyama, Yukiko Baba, Taketo Yamada, Shohei Egami, Takayuki Hoshii, Atsushi Hirao, Satoshi Matsuda, Shigeo Koyasu
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  ABSTRACT: The PI3K-Akt-mTORC1 axis contributes to the activation, survival, and proliferation of CD4(+) T cells upon stimulation through TCR and CD28. Here, we demonstrate that the suppression of this axis by deletion of p85α or PI3K/mTORC1 inhibitors as well as T cell-specific deletion of raptor, an essential component of mTORC1, impairs Th17 differentiation in vitro and in vivo in a S6K1/2-dependent fashion. Inhibition of PI3K-Akt-mTORC1-S6K1 axis impairs the downregulation of Gfi1, a negative regulator of Th17 differentiation. Furthermore, we demonstrate that S6K2, a nuclear counterpart of S6K1, is induced by the PI3K-Akt-mTORC1 axis, binds RORγ, and carries RORγ to the nucleus. These results point toward a pivotal role of PI3K-Akt-mTORC1-S6K1/2 axis in Th17 differentiation.
  Cell reports. 04/2012; 1(4):360-73.
• Article: Autoimmunity against M₂muscarinic acetylcholine receptor induces myocarditis and leads to a dilated cardiomyopathy-like phenotype.

  Akihiro Yoshizawa, Shigenori Nagai, Yukiko Baba, Taketo Yamada, Minoru Matsui, Hikaru Tanaka, Shun-ichiro Miyoshi, Masayuki Amagai, Tsutomu Yoshikawa, Keiichi Fukuda, Satoshi Ogawa, Shigeo Koyasu
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  ABSTRACT: Patients with dilated cardiomyopathy (DCM) often have autoantibodies against cardiac antigens including the M(2) muscarinic acetylcholine receptor (M(2)R). To elucidate the role of autoimmunity against M(2)R in disease development, we induced an immune response against M(2)R by adoptive transfer into Rag2(-/-) mice of splenocytes from M(2)R(-/-) mice immunized with a recombinant M(2)R protein. T lymphocytes transiently infiltrated the heart in recipient mice followed by morphological changes in cardiomyocytes. These mice produced IgG antibodies against M(2)R, which bound to cardiomyocytes in vivo and decreased the amplitude of calcium signals in isolated rat cardiomyocytes in vitro. Recipient mice showed increased heart weights associated with increased intraventricular diameter, decreased systolic function, and increased action potential duration, which are characteristics of DCM. Our results suggest that myocarditis and DCM associated with the presence of anti-M(2)R antibodies are autoimmune diseases with a risk of progressing to the terminal stage. Our mouse model will be useful in the analysis of the molecular mechanisms of disease progression and the development of new therapies for DCM.
  European Journal of Immunology 02/2012; 42(5):1152-63. · 5.10 Impact Factor
• Article: Listerial invasion protein internalin B promotes entry into ileal Peyer's patches in vivo.

  Sayuri Chiba, Takeshi Nagai, Toshiyuki Hayashi, Yukiko Baba, Shigenori Nagai, Shigeo Koyasu
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  ABSTRACT: Listeria monocytogenes (Lm) invades the host intestine using listerial invasion proteins, internalins. The in vivo role of internalin A (InlA) and internalin B (InlB) is reported here. Intragastric (i.g.) administration and ligated loop assays with ΔinlB-Lm demonstrated that a lack of InlB significantly attenuates the invasive ability of Lm into various organs. On the other hand, InlA(m)-Lm expressing a mutant InlA with two substitutions, S192N and Y369S, which has been reported to increase the affinity of InlA to mouse E-cadherin, resulted in little increase in intestinal infection according to both ligated loop and i.g. infection assays. Lm preferentially enters ileal Peyer's patch (PP) via M cells and ΔinlB-Lm showed severely reduced ability to invade though these cells. The present results reveal the importance of InlB, which accelerates listerial invasion into M cells on ileal PPs in vivo.
  Microbiology and Immunology 02/2011; 55(2):123-9. · 1.30 Impact Factor
• Article: Critical roles of NK and CD8+ T cells in central nervous system listeriosis.

  Toshiyuki Hayashi, Shigenori Nagai, Hideki Fujii, Yukiko Baba, Eiji Ikeda, Takeshi Kawase, Shigeo Koyasu
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  ABSTRACT: Listeria monocytogenes (LM) causes a life-threatening infectious disease affecting the brain of humans and domestic animals. Unfortunately, no adequate murine models for CNS listeriosis exist. Using intraparenchymal injection, we have established a new murine model for CNS listeriosis. Injection of a small volume of bacterial suspension limits the bacteria to the brain parenchyma with no leakage into the ventricular system. This new method enabled us to investigate the progression of and recovery from listerial brain infection, revealing roles for both innate and adaptive immune cells in CNS listeriosis. In the early phase of CNS listeriosis, NK cell-derived IFN-gamma is a critical cytokine in the limitation of bacterial growth by the host defense. During the later phase, CD8(+) but not CD4(+) T cells play a critical role and LM-specific CD8(+) T cells kill LM-infected microglia. Thus, innate and adaptive immune responses combine to successfully eliminate bacteria from the brain.
  The Journal of Immunology 06/2009; 182(10):6360-8. · 5.79 Impact Factor
• Source

  Available from: pnas.org

  Article: Role of Peyer's patches in the induction of Helicobacter pylori-induced gastritis.

  Shigenori Nagai, Hitomi Mimuro, Taketo Yamada, Yukiko Baba, Kazuyo Moro, Tomonori Nochi, Hiroshi Kiyono, Toshihiko Suzuki, Chihiro Sasakawa, Shigeo Koyasu
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  ABSTRACT: Helicobacter pylori is a Gram-negative spiral bacterium that causes gastritis and peptic ulcer and has been implicated in the pathogenesis of gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. Although Th1 immunity is involved in gastritis and the accumulation of H. pylori-specific CD4(+) T cells in the H. pylori-infected gastric mucosa in human patients, how T cells are primed with H. pylori antigens is unknown because no apparent lymphoid tissues are present in the stomach. We demonstrate here that Peyer's patches (PPs) in the small intestine play critical roles in H. pylori-induced gastritis; no gastritis is induced in H. pylori-infected mice lacking PPs. We also observed that the coccoid form of H. pylori is phagocytosed by dendritic cells in PPs. We propose that H. pylori converts to the coccoid form in the anaerobic small intestine and stimulates the host immune system through PPs.
  Proceedings of the National Academy of Sciences 06/2007; 104(21):8971-6. · 9.68 Impact Factor