Su-Man Kim

Bacterial β-(1,3)-glucan prevents DSS-induced IBD by restoring the reduced population of regulatory T cells.

Bacterial β-(1,3)-glucan has more advantages in terms of cost, yield and efficiency than that derived from mushrooms, plants, yeasts and fungi. We have previously developed a novel and high-yield β-(1,3)-glucan produced by Agrobacterium sp. R259. This study aimed to elucidate the functional mechanism and therapeutic efficacy of bacterial β-(1,3)-glucan in dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD).Mice were orally pretreated with bacterial β-(1,3)-glucan at daily doses of 2.5 or 5mg/kg for 2 weeks. After 6 days of DSS treatment, clinical assessment of IBD severity and expression of pro-inflammatory cytokines were evaluated. In vivo cell proliferation was examined by immunohistochemistry using Ki-67 and ER-TR7 antibodies. The frequency of regulatory T cells (Tregs) was analyzed by flow cytometry. Natural killer (NK) activity and IgA level were evaluated using NK cytotoxicity assay and ELISA.The deterioration of body weight gain, colonic architecture, disease score and histological score was recovered in DSS-induced IBD mice when pretreated with bacterial β-(1,3)-glucan. The recruitment of macrophages and the gene expression of proinflammatory cytokines, such as IL-1β, IL-6 and IL-17A/F, were markedly decreased in the colon of β-(1,3)-glucan-pretreated mice. β-(1,3)-Glucan induced the recovery of Tregs in terms of their frequency in DSS-induced IBD mice. Intriguingly, β-(1,3)-glucan reversed the functional defects of NK cells and excessive IgA production in DSS-induced IBD mice.We conclude that bacterial β-(1,3)-glucan prevented the progression of DSS-induced IBD by recovering the reduction of Tregs, functional defect of NK cells and excessive IgA production.

Cutaneous abscess by Trichosporon asahii developing on a steroid injection site in a healthy adult

We report a rare case of cutaneous abscess by Trichosporon asahii in an immunocompetent adult. A 31‐year‐old Korean woman presented to our hospital with a cutaneous abscess. She had received an intralesional steroid injection 4 months earlier on the site of a hypertrophic scar. Direct sequencing of the intergenic spacer regions of the rRNA genes identified T. asahii. The decreased local immunity after the steroid injection might have triggered the infection by T. asahii. A cutaneous abscess formation by T. asahii in an immunocompetent patient is an unusual cutaneous finding that to our knowledge has not been reported previously. The local immune reaction of the skin is important for the prevention of Trichosporon infection.

The association of naevus lipomatosus with pilosebaceous abnormalities including fibrofolliculoma

SIR, Naevus lipomatosus, also known as naevus lipomatosus cutaneus superficialis, has infrequently been reported to be associated with pilosebaceous abnormalities such as hypertrophic pilosebaceous units or perifollicular fibrosis. However, it is not yet known whether or not this is a true or a coincidental association. Naevus lipomatosus is a rare hamartomatous lesion, first described by Hoffmann and Zurhelle in 1921, characterized histopathologically by ectopic adipose tissue in the dermis, and clinically by a usually smooth, but sometimes wrinkled or verrucoid, surface. We report a patient with naevus lipomatosus associated with pilosebaceous abnormalities including fibrofolliculoma, which suggests that naevus lipomatosus is a connective tissue naevus involving abnormalities of mesenchymal and epithelial components. A 5-year-old Korean boy presented with asymptomatic skin-coloured soft lobulated plaques on the upper chest, which had been present since birth and had shown no change in shape. His personal and family medical histories were noncontributory. Examination showed several skin-coloured to yellowish soft grouped plaques with multiple umbilicated follicular papules on the surface, linearly distributed on the upper chest just below the neck (Fig. 1a). Laboratory examinations, including full blood count, urinalysis, serum chemistry and chest X-ray, were normal. Lesional skin biopsy showed deposition of mature fatty tissues in the dermis, thickening of collagen bundles and an increase in blood vessels in the dermis. Interestingly, there were well-circumscribed proliferations of basophilic loose connective tissue including mucin around hair follicles in which epithelial strands anastomosed each other. Another portion of the dermis showed dilated follicular cysts containing keratin debris (Fig. 1b). A diagnosis of naevus lipomatosus-associated pilosebaceous abnormalities including fibrofolliculoma was established, and the lesions were removed surgically. Naevus lipomatosus exists clinically as solitary or multiple (classic) types. The solitary form consists of isolated papules or nodules anywhere on the body, but usually on the trunk. In the multiple form, the lesions are usually congenital and manifest as soft nontender skin-coloured or yellow papules or nodules which coalesce into plaques. The site of predilection of the multiple form is the pelvic girdle area; however, a few cases have occurred in the scalp, shoulder, thorax, abdomen and face. Lesion surfaces are usually smooth, but variable features have been reported, such as cerebriform shapes, peau d’orange surface, comedo-like plugs, verrucous papules, hairiness and an association with haemangioma. In our patient, the lesion was atypical in that it showed umbilicated follicular papules on its surface, and it occurred at an unusual site, the upper chest just below the neck. The pathogenesis of naevus lipomatosus is unknown. Although the origin of dermal fat may be vascular endothelial cells or perivascular mesenchymal cells, there are varying amounts of other connective tissue components. Manifestations include collagen bundle thickening, a superficial reduction and a deeper increase in elastic fibres, and increased numbers of fibroblasts, mononuclear cells and blood vessels. Weedon placed naevus lipomatosus within the category of connective tissue naevi, and Orteu et al. also suggested a considerable overlap with connective tissue naevi. Naevus lipomatosus associated with an anomaly of the pilosebaceous unit has rarely been reported. Inoue et al. reported follicular papules and hypertrichosis on the surface, in which there was a prominent increase in the number of hair follicles with hypertrophic sebaceous glands histopathologically, and suggested that epithelial components are involved in

Formaldehyde exposure impairs the function and differentiation of NK cells.

We investigated the cytotoxic effects of formaldehyde (FA) on lymphocytes. FA-exposed mice showed a profound reduction not only in the number of natural killer (NK) cells but also in the expression of NK cell-specific receptors, but these mice did not exhibit decreases in the numbers of T or B lymphocytes. FA exposure also induced decreases in NK cytolytic activity and in the expression of NK cell-associated genes, such as IFN-γ, perforin and CD122. To determine the effect of FA on tumorigenicity, C57BL/6 mice were subcutaneously injected with B16F10 melanoma cells after FA exposure. The mass of the B16F10 tumor and the concentration of extravascular polymorphonuclear leukocytes were greater than those in unexposed tumor-bearing control mice. The number and cytolytic activity of NK cells were also reduced in B16F10 tumor-bearing mice exposed to FA. To determine how FA reduces the NK cell number, NK precursor (pNK) cells were treated with FA, and the differentiation status of the NK cells was analyzed. NK cell differentiation was impaired by FA treatment in a concentration-dependent manner. These findings indicate that FA exposure may promote tumor progression by impairing NK cell function and differentiation.

A case of hyperpigmented mycosis fungoides: a rare variant

© 2007 The Authors 983 JEADV 2007, 21, 977–1010 Journal compilation

Dapsone hypersensitivity syndrome with circulating 190-kDa and 230-kDa autoantibodies

Dapsone has potent anti‐inflammatory effects, and is used in the treatment of leprosy, cutaneous vasculitis, neutrophilic dermatoses, and dermatitis herpetiformis and other blistering disorders. However, it may cause severe adverse reactions such as hypersensitivity syndrome, which is characterized by fever, skin rash, hepatitis and lymphadenopathy. We report a 44‐year‐old female Korean patient with dapsone hypersensitivity syndrome (DHS) that presented as a bullous skin eruption. The patient had a 1‐year history of urticarial vasculitis, treated with antihistamines, prednisolone and dapsone. Although the skin lesions improved, she reported fever, nausea, abdominal pain, jaundice, fatigue and skin rashes. On physical examination, there were generalized erythematous macules and purpura with facial oedema that developed into vesicles on the upper limbs. Histological examination of a skin biopsy of a vesicular lesion found subepidermal oedema with a mixed inflammatory cell infiltrate, including eosinophils in the dermis. Indirect immunofluorescence testing using normal foreskin as substrate revealed IgG deposits in the basement membrane zone. Circulating autoantibodies against antigens of 190 and 230 kDa were found by immunoblotting analysis using epidermal extracts. This case illustrates DHS with the formation of circulating autoantibodies.

Fatal disseminated angioinvasive Fusarium falciforme infection in a patient with acute myeloid leukaemia

WHO–EORTC classification for cutaneous lymphomas. Among fewer than 50 cases of GSS reported in the English language literature to date, extracutaneous involvement of GSS has rarely been described; manifestations included granulomatous lymphadenitis and granuloma formation in enlarged spleen, liver and bone marrow. To the best of our knowledge, this is the second case in which clonal TCR-c rearrangements were detected in the affected lymph node. In 2005, an analogous case was reported by Liu et al. Given that lymph nodes in patients with GSS are only rarely subjected to morphological and molecular biological investigation, the extent of extracutaneous involvement in GSS may currently be underestimated.

TREM2 promotes Aβ phagocytosis by upregulating C/EBPα-dependent CD36 expression in microglia

TREM2 plays a critical role in the alleviation of Alzheimer’s disease by promoting Aβ phagocytosis by microglia, but the detailed molecular mechanism underlying TREM2-induced direct phagocytic activity of Aβ remains to be revealed. We found that learning and memory functions were improved in aged TREM2 TG mice, with the opposite effects in KO mice. The amount of phagocytosed Aβ was significantly reduced in the primary microglia of KO mice. CD36 expression in primary microglia was greater in TG than in WT mice but was substantially decreased in KO mice. The expression of C/EBPα, an upstream transcriptional activator of CD36, was also elevated in primary microglia of TG mice but decreased in KO mice. The transcription of CD36 was markedly increased by TREM2 overexpression, and this effect was suppressed by a mutation of the C/EBPα binding site on the CD36 promoter. The TREM2-induced expression of CD36 and C/EBPα was inhibited by treatment with PI3K/AKT signaling blockers, and phosphorylation of AKT was elevated in TREM2-overexpressing BV2 cells. The present study provides evidence that TREM2 is required for preventing loss of memory and learning in Alzheimer’s disease by regulating C/EBPα-dependent CD36 expression and the consequent Aβ phagocytosis.

The flavonoid hesperidin exerts anti-photoaging effect by downregulating matrix metalloproteinase (MMP)-9 expression via mitogen activated protein kinase (MAPK)-dependent signaling pathways

BackgroundHesperidin is a flavonoid with antioxidant, anti-inflammatory, and immune modulatory activities. Photoaging is a consequence of chronic exposure to the sun and ultraviolet (UV) radiation. This study was designed to evaluate the efficacy of hesperidin against photoaging of dorsal skin in hairless mice.MethodsHairless male mice (6-week-old) were divided into three groups (n = 7): control, UVB-treated vehicle, and UVB-treated hesperidin groups. UVB-irradiated mice from hesperidin group were orally administered 0.1 mL of water containing 100 mg/kg body weight per day hesperidin.ResultsThe mean length and depth of wrinkles in the UVB-treated hesperidin group significantly improved after the oral administration of hesperidin, which significantly inhibited the increase in epidermal thickness and epidermal hypertrophy (P < 0.05). UVB irradiation of mice induced epidermal barrier dysfunction including an increase in the transepidermal water loss (TEWL); however, hesperidin decreased the TEWL. UVB irradiation increased the expression of MMP-9 and pro-inflammatory cytokines whereas UVB-treated hesperidin group showed reduced expression. These results indicate that hesperidin showed anti-photoaging activity in the UVB-irradiated hairless mice. In conclusion, hesperidin inhibited the UVB-induced increase in skin thickness, wrinkle formation, and collagen fiber loss in male hairless mice.ConclusionsThese results suggest that hesperidin shows potent anti-photoaging activity by regulating MMP-9 expression through the suppression of MAPK-dependent signaling pathways.

Axl acts as a tumor suppressor by regulating LIGHT expression in T lymphoma

Axl is an oncogenic receptor tyrosine kinase that plays a role in many cancers. LIGHT (Lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells) is a ligand that induces robust anti-tumor immunity by enhancing the recruitment and activation of effector immune cells at tumor sites. We observed that mouse EL4 and human Jurkat T lymphoma cells that stably overexpressed Axl also showed high expression of LIGHT. When Jurkat-Axl cells were treated with Gas6, a ligand for Axl, LIGHT expression was upregulated through activation of the PI3K/AKT signaling pathway and transcriptional induction by Sp1. The lytic activity of cytotoxic T lymphocytes and natural killer cells was enhanced by EL4-Axl cells. In addition, tumor volume and growth were markedly reduced due to enhanced apoptotic cell death in EL4-Axl tumor-bearing mice as compared to control mice. We also observed upregulated expression of CCL5 and its receptor, CCR5, and enhanced intratumoral infiltration of cytotoxic T lymphocytes and natural killer cells in EL4-Axl-bearing mice as compared to mock controls. These data strongly suggested that Axl exerts novel tumor suppressor effects by inducing upregulation of LIGHT in the tumor microenvironment of T lymphoma.