start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=19 article-no= start-page=11035 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220920 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immune State Conversion of the Mesenteric Lymph Node in a Mouse Breast Cancer Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Secondary lymphoid tissues, such as the spleen and lymph nodes (LNs), contribute to breast cancer development and metastasis in both anti- and pro-tumoral directions. Although secondary lymphoid tissues have been extensively studied, very little is known about the immune conversion in mesenteric LNs (mLNs) during breast cancer development. Here, we demonstrate inflammatory immune conversion of mLNs in a metastatic 4T1 breast cancer model. Splenic T cells were significantly decreased and continuously suppressed IFN-gamma production during tumor development, while myeloid-derived suppressor cells (MDSCs) were dramatically enriched. However, T cell numbers in the mLN did not decrease, and the MDSCs only moderately increased. T cells in the mLN exhibited conversion from a pro-inflammatory state with high IFN-gamma expression to an anti-inflammatory state with high expression of IL-4 and IL-10 in early- to late-stages of breast cancer development. Interestingly, increased migration of CD103(+)CD11b(+) dendritic cells (DCs) into the mLN, along with increased (1 -> 3)-beta-D-glucan levels in serum, was observed even in late-stage breast cancer. This suggests that CD103(+)CD11b(+) DCs could prime cancer-reactive T cells. Together, the data indicate that the mLN is an important lymphoid tissue contributing to breast cancer development. en-copyright= kn-copyright= en-aut-name=ShigehiroTsukasa en-aut-sei=Shigehiro en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UenoMaho en-aut-sei=Ueno en-aut-mei=Maho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KijihiraMayumi en-aut-sei=Kijihira en-aut-mei=Mayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakahashiRyotaro en-aut-sei=Takahashi en-aut-mei=Ryotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UmemuraChiho en-aut-sei=Umemura en-aut-mei=Chiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TahaEman A. en-aut-sei=Taha en-aut-mei=Eman A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KurosakaChisaki en-aut-sei=Kurosaka en-aut-mei=Chisaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AsayamaMegumi en-aut-sei=Asayama en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MurakamiHiroshi en-aut-sei=Murakami en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SatohAyano en-aut-sei=Satoh en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakamuraYoshimasa en-aut-sei=Nakamura en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FutamiJunichiro en-aut-sei=Futami en-aut-mei=Junichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MasudaJunko en-aut-sei=Masuda en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Research Institute for Biomedical Sciences, Tokyo University of Science kn-affil= affil-num=2 en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University kn-affil= affil-num=3 en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University kn-affil= affil-num=8 en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=11 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=12 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=13 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=breast cancer cells kn-keyword=breast cancer cells en-keyword=dendritic cells kn-keyword=dendritic cells en-keyword=mesenteric lymph node kn-keyword=mesenteric lymph node en-keyword=myeloid-derived suppressor cells kn-keyword=myeloid-derived suppressor cells END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=9 article-no= start-page=1919 end-page=1933 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200521 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=G‐CSF‐dependent neutrophil differentiation requires downregulation of MAPK activities through the Gab2 signaling pathway en-subtitle= kn-subtitle= en-abstract= kn-abstract=Granulocyte colony‐stimulating factor (G‐CSF) stimulation of myeloid cells induced tyrosine‐phosphorylation of cellular proteins. One of the tyrosine‐phosphorylated proteins was found to be a scaffold protein, Grb2‐associated binding protein 2 (Gab2). Another member of Gab family protein, Gab3, was exogenously overexpressed in neutrophil progenitor cells to make the Gab3 protein to compete with the endogenous Gab2 for the G‐CSF‐dependent signaling. In Gab3‐overexpressed cells, the level of tyrosine phosphorylation of endogenous Gab2 by G‐CSF stimulation was markedly downregulated, while the phosphorylation of Gab3 was significantly enhanced. The Gab3‐overexpressed cells continuously proliferated in the medium containing G‐CSF and lost the ability to differentiate to the mature neutrophil, characterized by the lobulated nucleus. The G‐CSF stimulation‐dependent tyrosine phosphorylation of Gab3, the association of SHP2 to Gab3 and the following mitogen‐activated protein kinase (MAPK) activation were prolonged in the Gab3‐overexpressed cells, compared to the parental cells, where the binding of SHP2 to Gab2 protein and thereby the activation of MAPK were not sustained after G‐CSF stimulation. Inhibition of MAPK by pharmaceutical inhibitor restored the Gab3‐overexpressed cells to the ability to differentiate to mature neutrophil. Therefore, G‐CSF‐dependent Gab2 phosphorylation and following its downregulation led the short‐term MAPK activation. The downregulation of MAPK after transient Gab2 phosphorylation was necessary for the consequent neutrophil differentiation induced by G‐CSF stimulation. en-copyright= kn-copyright= en-aut-name=ZhaoXianglin en-aut-sei=Zhao en-aut-mei=Xianglin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawanoShun‐ichiro en-aut-sei=Kawano en-aut-mei=Shun‐ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MasudaJunko en-aut-sei=Masuda en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MurakamiHiroshi en-aut-sei=Murakami en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil= Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=granulocyte kn-keyword=granulocyte en-keyword=MAP kinase kn-keyword=MAP kinase en-keyword=negative feedback kn-keyword=negative feedback en-keyword=phosphorylation kn-keyword=phosphorylation en-keyword=scaffold protein kn-keyword=scaffold protein en-keyword=SHP2 kn-keyword=SHP2 END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=184 article-no= start-page=E175 end-page=E176 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191125 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Glycerol 3-Phosphate Dehydrogenase (GPD2) Regulates Glucose Oxidation in Bacterial Lipopolysaccharide (LPS)-Stimulated Macrophages en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MasudaJunko en-aut-sei=Masuda en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=Macrophages kn-keyword=Macrophages en-keyword=bacterial lipopolysaccharide (LPS) kn-keyword=bacterial lipopolysaccharide (LPS) en-keyword=Glycerol 3-phosphate dehydrogenase (GPD2) kn-keyword=Glycerol 3-phosphate dehydrogenase (GPD2) END