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Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) expressed in T cells may regulate immune responses in the gut. In addition to T cells, B cells are also an important population in the gut-associated lymphoid tissues that orchestrate mucosal homeostasis. However, the role of CEACAM1 in B cells has not been elucidated. We herein analyzed mature B cells to determine the functions of CEACAM1. Flow cytometry revealed high expression of CEACAM1 on B cells in secondary lymphoid tissues. Cytokine production induced by activation of B cell receptor (BCR) signaling was suppressed by CEACAM1 signaling in contrast to that associated with either Toll-like receptor 4 or CD40 signaling. Confocal microscopy revealed co-localization of CEACAM1 and BCR when activated with anti-Igμ F(ab’)2 fragment. Overexpression of CEACAM1 in a murine B cell line, A20, resulted in reduced expressions of activation surface markers with decreased Ca2+ influx after BCR signal activation. Overexpression of CEACAM1 suppressed BCR signal cascade in A20 cells in association with decreased spontaneous proliferation. Our results suggest that CEACAM1 can regulate BCR-mediated mature B cell activation in lymphoid tissues. Therefore, further studies of this molecule may lead to greater insights into the mechanisms of immune responses within peripheral tissues and the potential treatment of inflammatory diseases.

ObjectiveAlthough immunoglobulin A (IgA) is abundantly expressed in the gut and known to be an important component of mucosal barriers against luminal pathogens, its precise function remains unclear. Therefore, we tried to elucidate the effect of IgA on gut homeostasis maintenance and its mechanism.DesignWe generated various IgA mutant mouse lines using the CRISPR/Cas9 genome editing system. Then, we evaluated the effect on the small intestinal homeostasis, pathology, intestinal microbiota, cytokine production, and immune cell activation using intravital imaging.ResultsWe obtained two lines, with one that contained a tm/tm) and the other that lacked the most constant region of the IgH α chain, which resulted in the deficiency of IgA production (IgA−/−). IgA−/− exhibited spontaneous inflammation in the ileum but not the other parts of the gastrointestinal tract. Associated with this, there were significantly increased lamina propria CD4+ T cells, elevated productions of IFN-γ and IL-17, increased ileal segmented filamentous bacteria and skewed intestinal microflora composition. Intravital imaging using Ca2+ biosensor showed that IgA−/− had elevated Ca2+ signalling in Peyer’s patch B cells. On the other hand, IgAtm/tm seemed to be normal, suggesting that the IgA cytoplasmic tail is dispensable for the prevention of the intestinal disorder.ConclusionIgA plays an important role in the mucosal homeostasis associated with the regulation of intestinal microbiota and protection against mucosal inflammation especially in the ileum.

The effect of the lithium trifluoromethanesulfonate (LiCF3SO3) addition on the structure and properties for binary blends of poly(methyl methacrylate) (PMMA) and a random copolymer composed of vinyl butyral and vinyl alcohol, that is denoted as PVB in this paper, was evaluated. Although PMMA and PVB are immiscible, the LiCF3SO3 addition enhances the compatibility/miscibility by the ion-dipole interaction between lithium cation and both polymer chains. Only single peak ascribed to the glass-to-rubber transition is detected in the tensile loss modulus curve for PMMA/PVB/LiCF3SO3 (70/30/20), although there are distinct double peaks for PMMA/PVB (70/30). This result demonstrates that the salt, LiCF3SO3, acts as a compatibilizer. Furthermore, the salt addition enhances the storage modulus in the glassy region and the heat resistance due to the high-temperature-shift of glass transition temperature. The blend containing LiCF3SO3 is highly transparent and shows a significantly small value of the stress-optical coefficient in the glassy state, which are required for various optical films used for display, such as polarizer protective film.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) expressed in T cells may regulate immune responses in the gut. In addition to T cells, B cells are also an important population in the gut-associated lymphoid tissues that orchestrate mucosal homeostasis. However, the role of CEACAM1 in B cells has not been elucidated. We herein analyzed mature B cells to determine the functions of CEACAM1. Flow cytometry revealed high expression of CEACAM1 on B cells in secondary lymphoid tissues. Cytokine production induced by activation of B cell receptor (BCR) signaling was suppressed by CEACAM1 signaling in contrast to that associated with either Toll-like receptor 4 or CD40 signaling. Confocal microscopy revealed co-localization of CEACAM1 and BCR when activated with anti-Igμ F(ab')

Single-walled carbon nanotubes (SWNTs) with lengths of several hundred nanometers were crystallized from dilute solutions, and slender lath-shaped SWNT crystals were obtained. The SWNTs were oriented along the long axis of the lath-shaped crystal, and the obtained crystals were two-dimensional crystals comprising hexagonally close-packed SWNTs. A relatively long SWNT acted as a crystalline nucleus. The length of the SWNT used for crystallization affected the morphology and growth rate of the crystals. Higher crystallization temperature shortened the time to precipitation, and the diffusion of SWNTs dominated the crystal growth of SWNT crystals. Because the short SWNTs were rigid with a wide length distribution, their tube ends were inevitably included in the crystals, resulting in crystal defects, such as lattice curvature and edge dislocations. These defects were directly observed by high-resolution electron microscopy. The mechanism for the crystallization of the SWNTs was proposed based on the observed morphologies, crystal defects, and crystallization process.

Background It has been recently shown that the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) expressed in T cells may regulate immune responses in the gut. Moreover, it has also been reported that the treatments with either an agonistic monoclonal antibody (mAb) or natural ligands for this molecule can suppress colitis severity in murine models of inflammatory bowel diseases (IBD). On the other hand, in addition to T cells, B cells are also an important population in the gut-associated lymphoid tissues (GALT) that orchestrate mucosal homeostasis. However, the role of CEACAM1 in B cells has not been elucidated. Methods We analysed primary B-cell subsets in the lymphoid tissues of wild-type C57BL6 mice as well as a murine B-cell line, A20, to determine the expressions and functions of CEACAM1. Results FACS analysis of the lymphocyte subsets isolated from secondary lymphoid tissues such as spleen, mesenteric lymph nodes and Peyer’s patches of C57BL6 revealed higher expression level of CEACAM1 on B-cell surface than that of T cells. Bone marrow analysis showed that such CEACAM1 expression was increased during maturation and differentiation process of B cells. When isolated splenic B cells were stimulated with LPS, anti-CD40 or anti-μ chain Abs in the presence of agonistic anti-CEACAM1 mAb, the usual increased cytokine productions (such as IL-4 and IL-5 by activation via B cell receptor (BCR) signalling) were specifically suppressed by CEACAM1 signalling rather than B-cell activations via either TLR4 or CD40 signalling. Immunofluorescent studies using confocal microscopy revealed co-localisation of CEACAM1 and BCR when B cells were activated with anti-μ chain Ab. Given these results, A20 cells were transfected with CEACAM1 cDNA. Biochemical analysis showed that an inducible overexpression of CEACAM1 suppressed the BCR signalling in these cells when compared with that of vector alone-transfected control. Moreover, the overexpression of CEACAM1 in these cells resulted in reduced expressions of activation markers such as CD69, CD80, CD86, MHC-I and -II on the cell surface. These observations were associated with decreased Ca2+ influx and suppressed cytokine production by the overexpression of CEACAM1 after BCR signal activation. Conclusion These results suggest that CEACAM1 can regulate B-cell activation and differentiation specifically via BCR signalling in the lymphoid tissues. Therefore, this molecule can be a therapeutic target in IBD by regulating of both T-cell and B-cell activation in GALT.

Chronic diarrhea is one of the major symptoms in gastroenterology. However, this may be caused by pathologic conditions for which the diagnosis is critical. Villous atrophy, as an endoscopic lesion, accompanied by chronic diarrhea can occasionally be observed in the patients with inflammatory diseases of the gastrointestinal (GI) tract. Herein, we present a case with persistent diarrhea accompanied by intestinal wall thickening without any other significant endoscopic features other than villous atrophy in the jejunum and the ileum, where we diagnosed as an indolent T cell lymphoproliferative disorder (T-LPD) of the GI tract, defined in the 2016–2017 revised World Health Organization classification, via single-balloon enteroscopy (SBE). Interestingly, we found the same lymphocyte infiltration from the distal third portion of the duodenum, where gastroscopy could not reach, via SBE, even though no endoscopic findings were observed such as villous atrophy. Since infiltrating cells in the intestinal tissues were CCR4+, mogamulizumab was administered with resulting durable symptomatic remission for more than 2 years. Patients with persistent diarrhea may have serious small intestinal disorder including not only chronic inflammatory diseases but also lymphoid neoplasmic conditions including T-LPD of GI tract.

The effect of the addition of lithium trifluoromethanesulfonate (LiCF_3SO_3) on the linear viscoelastic properties, crystallization behavior, and mechanical properties of poly(lactic acid) (PLA) was studied. The glass transition temperature (T_g) was enhanced by adding LiCF_3SO_3, without any loss of transparency of the PLA. This was attributed to the ion-dipole interaction between the lithium cation and oxygen atom in the PLA carbonyl group. The interaction weakened at higher temperature. Consequently, the rheological terminal region was clearly detected, which suggested that the system possessed good melt-processability. The Young’s modulus and yield stress at room temperature were also enhanced by the addition of LiCF_3SO_3, although the toughness was reduced due to the brittle failure. Finally, the presence of LiCF_3SO_3 retarded the crystallization of PLA, because the segmental motion of the PLA chains was reduced.

Although previous studies have suggested that appendix seems to be involved in the colitis, the role of this in the pathogenesis remains unclear. In this study, we assessed the importance of appendiceal lymphoid follicles, specifically the cecal patches (CP) in mice, using an experimental colitis model. Treatment with oxazolone resulted in ulcerations particularly at CP with follicular expansion as well as colitis. The colitis was attenuated by either appendectomy or the absence of mature B cells. We therefore established an intravital imaging system accompanied by the fluorescence resonance energy transfer technology to analyze the dynamic immune response of CP B cells. Our observation revealed frequent Ca2+ signaling in CP B cells during the early phase of colitis development. These findings suggested that the CP B cells may be involved in the pathogenesis of colitis including inflammatory bowel diseases in humans.

We report a patient with ventral simultanagnosia, prosopagnosia for "unfamiliar faces" (dorsal prosopagnosia), spatial agraphia, and constructional disorder, particularly on the left spatial side, due to a lesion in the right posterior superior and middle temporal gyri and angular gyrus. The patient showed impairment of fundamental visual and visuospatial recognition, such as in object size, configuration, and horizontal point location, which probably underlay the mechanism of simultanagnosia and prosopagnosia. This case also suggests that the coexistence of simultanagnosia and prosopagnosia results from a right hemispheric insult, and damage to the temporoparietal area interrupts the incorporation of spatial information into object recognition. This disconnection of information flow, together with impaired object recognition per se, may impair the parallel processing of multiple objects, leading to object-by-object or part-by-part recognition.