Keisuke Kojima

Bio: Keisuke Kojima is an academic researcher from Kumamoto University. The author has contributed to research in topics: Bronchoalveolar lavage & Pulmonary function testing. The author has an hindex of 8, co-authored 18 publications receiving 258 citations.

Galectin-9 expands immunosuppressive macrophages to ameliorate T-cell-mediated lung inflammation.

Abstract: Galectin-9 (Gal-9) plays pivotal roles in the modulation of innate and adaptive immunity to suppress T-cell-mediated autoimmune models. However, it remains unclear if Gal-9 plays a suppressive role for T-cell function in non-autoimmune disease models. We assessed the effects of Gal-9 on experimental hypersensitivity pneumonitis induced by Trichosporon asahii. When Gal-9 was given subcutaneously to C57BL/6 mice at the time of challenge with T. asahii, it significantly suppressed T. asahii-induced lung inflammation, as the levels of IL-1, IL-6, IFN-gamma, and IL-17 were significantly reduced in the BALF of Gal-9-treated mice. Moreover, co-culture of anti-CD3-stimulated CD4 T cells with BALF cells harvested from Gal-9-treated mice on day 1 resulted in diminished CD4 T-cell proliferation and decreased levels of IFN-gamma and IL-17. CD11b(+)Ly-6C(high)F4/80(+) BALF Mphi expanded by Gal-9 were responsible for the suppression. We further found in vitro that Gal-9, only in the presence of T. asahii, expands CD11b(+)Ly-6C(high)F4/80(+) cells from BM cells, and the cells suppress T-cell proliferation and IFN-gamma and IL-17 production. The present results indicate that Gal-9 expands immunosuppressive CD11b(+)Ly-6C(high) Mphi to ameliorate Th1/Th17 cell-mediated hypersensitivity pneumonitis.

Galectin-9 attenuates acute lung injury by expanding CD14- plasmacytoid dendritic cell-like macrophages.

Abstract: Rationale: Galectin (Gal)-9 plays a crucial role in the modulation of innate and adaptive immunity.Objectives: To investigate whether Gal-9 plays a role in a murine acute lung injury (ALI) model.Methods: C57BL/6 mice were pretreated with Gal-9 by subcutaneous injection 24 and 48 hours before intranasal LPS inoculation.Measurements and Main Results: Gal-9 suppressed pathological changes of ALI induced by LPS. Gal-9 reduced levels of proinflammatory cytokines and chemokines, such as tumor necrosis factor (TNF)-α, IL-1β, IL-6, and keratinocyte-derived cytokine; decreased neutrophils; and increased IL-10 and CD11b+Gr-1+ macrophages in the bronchoalveolar lavage fluid of ALI mice. In Gal-9–deficient mice, pathological changes of ALI were exaggerated, and the number of neutrophils and the TNF-α level were increased. CD11b+Gr-1+ cells were increased in the spleen of both Gal-9–treated and phosphate-buffered saline (PBS)–treated ALI mice, but only Gal-9 increased the ability of CCR2-expressing macrophages to migr...

Favorable outcome with hemoperfusion of polymyxin B-immobilized fiber column for rapidly progressive interstitial pneumonia associated with clinically amyopathic dermatomyositis: report of three cases

Abstract: We present 3 cases of rapidly progressive interstitial pneumonia (RPIP) associated with clinically amyopathic dermatomyositis (C-ADM) that were treated with two courses of direct hemoperfusion with polymyxin B-immobilized fiber column (PMX-DHP). Despite initial treatment with high-dose corticosteroids, pulsed cyclophosphamide, and cyclosporine, the lung disease and hypoxemia deteriorated in all the patients. After PMX-DHP treatment, the PaO2/FiO2 ratio and serum LDH and KL-6 were improved, the abnormal shadows in chest high-resolution computed tomography (HRCT) scans gradually decreased, and, finally, all patients survived. These findings indicate that PMX-DHP treatment could be effective in the management of RPIP in patients with C-ADM in combination with conventional therapy.

Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T-CELL suppressive activity

Abstract: The induction of CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs) is an important immune-evading mechanism used by tumors. However, the exact nature and function of MDSCs remain elusive, especially because they constitute a heterogeneous population that has not yet been clearly defined. Here, we identified 2 distinct MDSC subfractions with clear morphologic, molecular, and functional differences. These fractions consisted of either mononuclear cells (MO-MDSCs), resembling inflammatory monocytes, or low-density polymorphonuclear cells (PMN-MDSCs), akin to immature neutrophils. Interestingly, both MO-MDSCs and PMN-MDSCs suppressed antigen-specific T-cell responses, albeit using distinct effector molecules and signaling pathways. Blocking IFN-gamma or disrupting STAT1 partially impaired suppression by MO-MDSCs, for which nitric oxide (NO) was one of the mediators. In contrast, while IFN-gamma was strictly required for the suppressor function of PMN-MDSCs, this did not rely on STAT1 signaling or NO production. Finally, MO-MDSCs were shown to be potential precursors of highly antiproliferative NO-producing mature macrophages. However, distinct tumors differentially regulated this inherent MO-MDSC differentiation program, indicating that this phenomenon was tumor driven. Overall, our data refine tumor-induced MDSC functions by uncovering mechanistically distinct MDSC subpopulations, potentially relevant for MDSC-targeted therapies.

Current Knowledge of Trichosporon spp. and Trichosporonosis

Abstract: SUMMARY Trichosporon spp. are basidiomycetous yeast-like fungi found widely in nature. Clinical isolates are generally related to superficial infections. However, this fungus has been recognized as an opportunistic agent of invasive infections, mostly in cancer patients and those exposed to invasive medical procedures. It is possible that the ability of Trichosporon strains to form biofilms on implanted devices, the presence of glucuronoxylomannan in their cell walls, and the ability to produce proteases and lipases are all factors likely related to the virulence of this genus and therefore may account for the progress of invasive trichosporonosis. Disseminated trichosporonosis has been increasingly reported worldwide and represents a challenge for both diagnosis and species identification. Phenotypic identification methods are useful for Trichosporon sp. screening, but only molecular methods, such as IGS region sequencing, allow the complete identification of Trichosporon isolates at the species level. Methods for the diagnosis of invasive trichosporonosis include PCR-based methods, Luminex xMAP technology, and, more recently, proteomics. Treating patients with trichosporonosis remains a challenge because of limited data on the in vitro and in vivo activities of antifungal drugs against clinically relevant species of the genus. Despite the mentioned limitations, the use of antifungal regimens containing triazoles appears to be the best therapeutic approach.

Hypersensitivity pneumonitis

Abstract: Hypersensitivity pneumonitis is a pulmonary disease with symptoms of cough and dyspnea resulting from the inhalation of an antigen to which the subject has been previously sensitized,such as microbes,animal or plant proteins and certain chemicals that form haptens.The radiologic findings include diffuse ground-glass opacification,small centrilobular nodules,air trapping,fibrosis and emphysema.Bronchoalveolar lavage fluid reveals a lymphocyte alveolitis with CD4/CD8 decrease.The histopathologic process consists of chronic inflammation of the bronchi and peribronchiolar tissue,often with poorly defined granulomas.The diagnosis usually rests on a variable combination of findings from history,clinical manifestation,radiography,serology,bronchoalveolar lavage fluid and lung biopsy.Treatment includes avoiding the allergen and systemic corticosteroids.The long-term prognosis is usually good. Key words: Hypersensitivity pneumonitis; Etiology; Clinical presentation; Diagnosis; Treatment

Diagnostic and therapeutic challenges.

Abstract: This case is submitted by Drs. Francisco J. Ascaso, Maria Rojo, and Enrique Minguez from the Department of Ophthalmology, “Lozano Blesa” University Clinic Hospital, Zaragoza, Spain, for the Diagnostic and Therapeutic Challenges Section of Retina; and commented by Dr. Steven M. Cohen, Clearwater, Flo