Signal-transducing adaptor protein-2 has a nonredundant role for IL-33-triggered mast cell activation

Signal-transducing adaptor protein (STAP)-2 is one of the STAP family adaptor proteins and ubiquitously expressed in a variety types of cells. Although STAP-2 is required for modification of Fc epsilon RI signal transduction in mast cells, other involvement of STAP-2 in mast cell functions is unknown, yet. In the present study, we mainly investigated functional roles of STAP-2 in IL-33-induced mast cell activation. In STAP-2-deficient, but not STAP-1-deficient, mast cells, IL-33-induced IL-6 and TNF-alpha production was significantly decreased compared with that of wild-type mast cells. In addition, STAP-2-deficiency greatly reduced TLR4-mediated mast cell activation and cytokine production. For the mechanisms, STAP-2 directly binds to IKK alpha after IL-33 stimulation, leading to elevated NF-kappa B activity. In conclusion, STAP-2, but not STAP-1, participates in IL-33-induced mast cells activation

Clinical and Genetic Investigation of a Japanese Family With Cardiac Fabry Disease: Identification of a Novel α-Galactosidase A Missense Mutation (G195V) (心臓Fabry病の1家族についての臨床的並びに遺伝的研究)

雑誌掲載版 J-STAGE掲載版使用 https://www.jstage.jst.go.jp/browse/-char/jaFabry病はα-galactosidase A遺伝子(GLA)の変異によるX染色体関連リソゾーム貯蔵障害に基づく疾患で、特発性肥大型心筋症に似た左室肥大を伴うことがある。本研究では三代にわたり本症患者が5名あった1家族の10名についてGLA変異を検査した。発端者は後壁基部の限局性菲薄化を伴う左室肥大があり、MR画像ではほぼ全周性にガドリニウム遅延増強(LGE)があった。LGEはα-galactosidase活性低下とともに著明化した。本研究でエクソン4に新しいミスセンス変異を発見した

Potential role of HTLV-1 Tax-specific cytotoxic t lymphocytes expressing a unique t-cell receptor to promote inflammation of the central nervous system in myelopathy associated with HTLV-1.

Human T-lymphotropic virus 1 (HTLV-1) infection causes two serious diseases: adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy (HAM). Immunological studies have revealed that HTLV-1 Tax-specific CD8+ cytotoxic T-cells (Tax-CTLs) in asymptomatic carriers (ACs) and ATL patients play an important role in the elimination of HTLV-1-infected host cells, whereas Tax-CTLs in HAM patients trigger an excessive immune response against HTLV-1-infected host cells infiltrating the central nervous system (CNS), leading to local inflammation. Our previous evaluation of HTLV-1 Tax301-309 (SFHSLHLLF)-specific Tax-CTLs (Tax301-309-CTLs) revealed that a unique T-cell receptor (TCR) containing amino acid (AA)-sequence motif PDR, was shared among HLA-A*24:02+ ACs and ATL patients and behaved as an eliminator by strong activity against HTLV-1. However, it remains unclear whether PDR+Tax301-309-CTLs also exist in HLA-A*24:02+ HAM patients and are involved in the pathogenesis of HAM. In the present study, by high-throughput TCR repertoire analysis technology, we revealed TCR repertoires of Tax301-309-CTLs in peripheral blood (PB) of HLA-A*24:02+ HAM patients were skewed, and a unique TCR-motif PDR was conserved in HAM patients (10 of 11 cases). The remaining case dominantly expressed (-DR, P-R, and PD-), which differed by one AA from PDR. Overall, TCRs with unique AA-sequence motifs PDR, or (-DR, P-R, and PD-) accounted for a total of 0.3-98.1% of Tax301-309-CTLs repertoires of HLA-A*24:02+ HAM patients. Moreover, TCR repertoire analysis of T-cells in the cerebrospinal fluid (CSF) from four HAM patients demonstrated the possibility that PDR+Tax301-309-CTLs and (-DR, P-R, and PD-)+Tax301-309-CTLs efficiently migrated and accumulated in the CSF of HAM patients fostering increased inflammation, although we observed no clear significant correlation between the frequencies of them in PB and the levels of CSF neopterin, a known disease activity biomarker of HAM. Furthermore, to better understand the potential function of PDR+Tax301-309-CTLs, we performed immune profiling by single-cell RNA-sequencing of Tax301-309-CTLs, and the result showed that PDR+Tax301-309-CTLs up-regulated the gene expression of natural killer cell marker KLRB1 (CD161), which may be associated with T-cell activation and highly cytotoxic potential of memory T-cells. These findings indicated that unique and shared PDR+Tax301-309-CTLs have a potential role in promoting local inflammation within the CNS of HAM patients

Hepatic Hodgkin lymphoma with delayed enhancement on CT and MRI

Hepatic Hodgkin lymphoma is a rare disease, characterized by the presence of abundant granulofibrous stroma, and its radiological features have rarely been described. We report a 67-year-old man, who presented with liver masses that showed apparent delayed enhancement, along with systemic lymphadenopathy and musculoskeletal lesions. Repeated percutaneous needle biopsy, however, failed to confirm the diagnosis, and surgical biopsy finally revealed small amount of Hodgkin cells and Reed-Sternberg cells. In this report, the radiological features of hepatic Hodgkin lymphoma will be presented and discussed, in correlation with its histological findings