Biology subjects

Yokote, K.

Publications and source records attributed to Yokote, K..

3 recordsLinked to original sources

bioRxiv2022

Semaphorin 3G exacerbates joint inflammation through the accumulation and proliferation of macrophages in the synovium

ObjectiveMethotrexate (MTX) is an anchor drug for rheumatoid arthritis (RA) treatment; however, the exact mechanisms by which MTX improves RA activity are still debatable. This study aimed to understand the roles of molecules whose expression is affected by MTX in RA patients and find novel therapeutic targets. MethodsCD4+ T cells from 28 treatment naive RA patients before and 3 months after the initiation of MTX treatment were subjected to DNA microarray analyses. The expression of Semaphorin 3G (Sema3G), as one of the differentially-expressed genes, and its receptor, Neuropilin-2 (Nrp2), was evaluated in RA synovium and collagen-induced arthritis (CIA) synovium. CIA and collagen antibody-induced arthritis (CAIA) were induced in Sema3G-deficient (Sema3G-/-) mice and control mice, and the clinical score, histological score, and serum cytokines were assessed. The migration and proliferation of Sema3G-stimulated bone marrow-derived macrophages (BMMs) were analyzed in vitro. The effect of local Sema3G administration during CAIA on the clinical score and the quantity of infiltrating macrophages was evaluated. ResultsThe expression of Sema3G in CD4+ T cells was downregulated by MTX treatment in RA patients. Sema3G was expressed in RA but not osteoarthritis synovium, and its receptor Nrp2 was mainly expressed on activated macrophages. Sema3G deficiency ameliorated CIA and CAIA. Sema3G stimulation enhanced the migration and proliferation of BMMs. The local administration of Sema3G deteriorated CAIA and increased infiltrating macrophages. ConclusionsUpregulation of Sema3G in RA synovium is a novel mechanism to deteriorate joint inflammation through the accumulation of macrophages. Key messagesSemaphorin 3G is expressed in the inflamed synovium in human and mice. The receptor of Semaphorin 3G is mainly expressed on M1 macrophages. Semaphorin 3G deteriorates inflammatory arthritis through macrophage proliferation and migration.

pathology↗

bioRxiv2021

Immunological features that determine the strength of antibody responses to BNT162b2 mRNA vaccine against SARS-CoV-2

We analyzed peripheral blood mononuclear cells (PBMCs) of each 20 individuals with a high anti-SARS-CoV-2 antibody titer and a low antibody titer out of 1,774 healthcare workers who received BNT162b2 mRNA vaccine. A higher antibody titer was associated with the frequencies of naive and transitional B cells before vaccination. In addition, fold changes in the frequency of activated CD8+ T cells upon vaccination were correlated with the antibody titers.

immunology↗

bioRxiv2021

Stem cell therapy for skin regeneration using mesenchymal stem cells derived from the progeroid Werner syndrome-specific iPS cells

Adult progeria, Werner syndrome (WS), is an autosomal recessive disorder that develops accelerated aging-associated symptoms after puberty. Refractory skin ulcer of limbs, which is one of the symptoms specific to WS, is seriously painful and sometimes results in amputation. In recent years, cell therapy using mesenchymal stem cells (MSCs) has been attracting attention; however, the effect of WS-derived MSCs on skin ulcers is still unclear. In this study, we generated iPS cells from a patient with WS and a normal subject, differentiated them into MSCs (WS- and NM-iMSC, respectively), and performed cell therapy to a refractory skin ulcer mouse model. As a result, WS-iMSC recapitulated premature senescence phenotypes in vitro. Upon subcutaneous injection around the wounds of mice, WS-iMSC was significantly inferior in wound healing effect compared to NM-iMSC. Proteome and transcriptome analysis revealed altered expression of genes related to angiogenesis, inflammation, and proliferation in WS-iMSC with remarkable downregulation of VEGF, a potent angiogenic factor. In addition, simultaneous administration of recombinant human VEGF and WS-iMSC improved the wound healing effect in vivo. These results indicate that the expression of angiogenic factors is reduced in WS-iMSC, and its supplementation restores the wound healing ability. This finding may pave the way to develop the treatment of intractable skin ulcers of WS.

cell biology↗