start-ver=1.4 cd-journal=joma no-vol=557 cd-vols= no-issue= article-no= start-page=199 end-page=205 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021611 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Adrenergic signaling promotes the expansion of cancer stem-like cells of malignant peripheral nerve sheath tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Malignant peripheral nerve sheath tumor (MPNST), a highly malignant tumor that arises in peripheral nerve tissues, is known to be highly resistant to radiation and chemotherapy. Although there are several reports on genetic mutations and epigenetic changes that define the pathogenesis of MPNST, there is insufficient information regarding the microenvironment that contributes to the malignancy of MPNST. In the present study, we demonstrate that adrenaline increases the cancer stem cell population in MPNST. This effect is mediated by adrenaline stimulation of beta-2 adrenergic receptor (ADRB2), which activates the Hippo transducer, YAP/TAZ. Inhibition and RNAi experiments revealed that inhibition of ADRB2 attenuated the adrenaline-triggered activity of YAP/TAZ and subsequently attenuated MPNST cells stemness. Furthermore, ADRB2-YAP/TAZ axis was confirmed in the MPNST patients’ specimens. The prognosis of patients with high levels of ADRB2 was found to be significantly worse. These data show that adrenaline exacerbates MPNST prognosis and may aid the development of new treatment strategies for MPNST. en-copyright= kn-copyright= en-aut-name=HuangRongsheng en-aut-sei=Huang en-aut-mei=Rongsheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakihiraShota en-aut-sei=Takihira en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueHirofumi en-aut-sei=Inoue en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshikawaSoichiro en-aut-sei=Yoshikawa en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HiyamaTakeshi en-aut-sei=Hiyama en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KamiyaAtsunori en-aut-sei=Kamiya en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Clinical Genetics and Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=MPNST kn-keyword=MPNST en-keyword=Cancer stem-like cells kn-keyword=Cancer stem-like cells en-keyword=ADRB2 kn-keyword=ADRB2 en-keyword=YAP/TAZ kn-keyword=YAP/TAZ END start-ver=1.4 cd-journal=joma no-vol=73 cd-vols= no-issue=1 article-no= start-page=24 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Connective tissue mast cells store and release noradrenaline en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mast cells are present in mucosal and connective tissues throughout the body. They synthesize and release a wide variety of bioactive molecules, such as histamine, proteases, and cytokines. In this study, we found that a population of connective tissue mast cells (CTMCs) stores and releases noradrenaline, originating from sympathetic nerves. Noradrenaline-storing cells, not neuronal fibers, were predominantly identified in the connective tissues of the skin, mammary gland, gastrointestinal tract, bronchus, thymus, and pancreas in wild-type mice but were absent in mast cell-deficient W-sash c-kit mutant KitW-sh/W-sh mice. In vitro studies using bone marrow-derived mast cells revealed that extracellular noradrenaline was taken up but not synthesized. Upon ionomycin stimulation, noradrenaline was released. Electron microscopy analyses further suggested that noradrenaline is stored in and released from the secretory granules of mast cells. Finally, we found that noradrenaline-storing CTMCs express organic cation transporter 3 (Oct3), which is also known as an extraneuronal monoamine transporter, SLC22A3. Our findings indicate that mast cells may play a role in regulating noradrenaline concentration by storing and releasing it in somatic tissues. en-copyright= kn-copyright= en-aut-name=OtaniYusuke en-aut-sei=Otani en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshikawaSoichiro en-aut-sei=Yoshikawa en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagaoKei en-aut-sei=Nagao en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Mast cells kn-keyword=Mast cells en-keyword=Connective tissue mast cells kn-keyword=Connective tissue mast cells en-keyword=Noradrenaline kn-keyword=Noradrenaline en-keyword=Immunoelectron microscopy kn-keyword=Immunoelectron microscopy en-keyword=SLC22A3 kn-keyword=SLC22A3 END start-ver=1.4 cd-journal=joma no-vol=2021 cd-vols= no-issue=43 article-no= start-page=e12804 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201030 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The role of basophils in acquired protective immunity to tick infestation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ticks are blood‐feeding ectoparasites that transmit a variety of pathogens to host animals and humans, causing severe infectious diseases such as Lyme disease. In a certain combination of animal and tick species, tick infestation elicits acquired immunity against ticks in the host, which can reduce the ability of ticks to feed on blood and to transmit pathogens in the following tick infestations. Therefore, our understanding of the cellular and molecular mechanisms of acquired tick resistance (ATR) can advance the development of anti‐tick vaccines to prevent tick infestation and tick‐borne diseases. Basophils are a minor population of white blood cells circulating in the bloodstream and are rarely observed in peripheral tissues under steady‐state conditions. Basophils have been reported to accumulate at tick‐feeding sites during re‐infestation in cattle, rabbits, guinea pigs and mice. Selective ablation of basophils resulted in a loss of ATR in guinea pigs and mice, illuminating the essential role of basophils in the manifestation of ATR. In this review, we discuss the recent advance in the elucidation of the cellular and molecular mechanisms underlying basophil recruitment to the tick‐feeding site and basophil‐mediated ATR. en-copyright= kn-copyright= en-aut-name=YoshikawaSoichiro en-aut-sei=Yoshikawa en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyakeKensuke en-aut-sei=Miyake en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KamiyaAtsunori en-aut-sei=Kamiya en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KarasuyamaHajime en-aut-sei=Karasuyama en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Inflammation, Infection and Immunity Laboratory, TMDU Advanced Research Institute, Tokyo Medical and Dental University (TMDU) kn-affil= affil-num=3 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Inflammation, Infection and Immunity Laboratory, TMDU Advanced Research Institute, Tokyo Medical and Dental University (TMDU) kn-affil= en-keyword=acquired immunity kn-keyword=acquired immunity en-keyword=basophil kn-keyword=basophil en-keyword=histamine kn-keyword=histamine en-keyword=IgE kn-keyword=IgE en-keyword=IL‐3 kn-keyword=IL‐3 en-keyword=mast cell kn-keyword=mast cell en-keyword=Tick kn-keyword=Tick END