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Objectives: Decreased sialylation of IgG-Fc glycans has been reported in autoimmune diseases, but its role in systemic lupus erythematosus (SLE) is not fully understood. In this study, we examined the pathogenicity of IgG desialylation and its association with Th17 in SLE using an animal model., Methods: B6SKG mice, which develop lupus-like systemic autoimmunity due to the ZAP70 mutation, were used to investigate the pathogenicity of IgG desialylation. The proportion of sialylated IgG was compared between B6SKG and wild-type mice with or without β-glucan treatment-induced Th17 expansion. Anti-interleukin (IL)-23 and anti-IL-17 antibodies were used to examine the role of Th17 cells in IgG glycosylation. Activation-induced cytidine deaminase-specific St6gal1 conditionally knockout (cKO) mice were generated to examine the direct effect of IgG desialylation., Results: The proportions of sialylated IgG were similar between B6SKG and wild-type mice in the steady state. However, IgG desialylation was observed after β-glucan-induced Th17 expansion, and nephropathy also worsened in B6SKG mice. Anti-IL-23/17 treatment suppressed IgG desialylation and nephropathy. Glomerular atrophy was observed in the cKO mice, suggesting that IgG desialylation is directly involved in disease exacerbation., Conclusions: IgG desialylation contributes to the progression of nephropathy, which is ameliorated by blocking IL-17A or IL-23 in an SLE mouse model., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: We aimed to clarify the clinical significance of serum levels of MMPs in interstitial lung disease (ILD) complicated with PM/DM (PM/DM-ILD)., Methods: We retrospectively analysed serum levels of seven subsets of MMPs in 52 PM/DM-ILD patients diagnosed at Kyoto University Hospital or Tenri Hospital from January 2005 to December 2014. The patients were sub-grouped based on the presence of anti-amimoacyl-tRNA synthetase antibody (anti-ARS antibody), anti-melanoma differentiation-associated protein 5 antibody (anti-MDA5 antibody) or lack of the antibodies (ARS-ILD, MDA5-ILD and other-ILD groups, respectively) and independently analysed. Eighteen PM/DM patients without ILD and 55 healthy control were also analysed. Associations between serum levels of MMPs and clinical findings including mortality were analysed., Results: Among the MMPs analysed, MMP-7 serum levels in the ARS-ILD group were significantly higher compared with those in any of the other groups of PM/DM patients or in healthy controls. On the other hand, in the MDA5-ILD group, serum MMP-7 levels >5.08 ng/ml were associated with worse overall survival both in univariate (P = 0.017; odds ratio 18.0; 95% CI 1.69, 192.00) and multivariate (P = 0.027; odds ratio 14.60; 95% CI 1.11, 192.00) analyses. Immunohistochemical analysis suggested that MMP-7 was expressed in type II alveolar epithelial cells adjacent to the fibrotic lesions., Conclusion: Serum MMP-7 levels were higher in anti-ARS antibody-positive PM/DM-ILD patients, while higher serum MMP-7 levels among anti-MDA5 antibody-positive PM/DM-ILD patients were associated with a worse prognosis. Fibrotic processes may be associated with the elevation of serum MMP-7 levels., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Mucosal-associated invariant T (MAIT) cells are innate-like T cells involved in the homeostasis of mucosal immunity; however, their role in inflammatory bowel disease (IBD) is unclear., Methods: Flow cytometry was used to enumerate peripheral blood MAIT cells in 88 patients with ulcerative colitis (UC), 68 with Crohn's disease (CD), and in 57 healthy controls. Immunohistochemistry identified MAIT cells in intestinal tissue samples from patients with UC (n = 5) and CD (n = 10), and in control colon (n = 5) and small intestine (n = 9) samples. In addition, expression of activated caspases by MAIT cells in the peripheral blood of 14 patients with UC and 15 patients with CD, and 16 healthy controls was examined., Results: Peripheral blood analysis revealed that patients with IBD had significantly fewer MAIT cells than healthy controls (P < 0.0001). The number of MAIT cells in the inflamed intestinal mucosae of patients with UC and CD was also lower than that in control mucosae (P = 0.0079 and 0.041, respectively). The number of activated caspase-expressing MAIT cells in the peripheral blood of patients with UC and CD was higher than that in healthy controls (P = 0.0061 and 0.0075, respectively), suggesting that the reduced MAIT cell numbers in IBD are associated with an increased level of apoptosis among these cells., Conclusions: The number of MAIT cells in the peripheral blood and inflamed mucosae of patients with UC and CD was lower than that in non-IBD controls. Also, MAIT cells from patients with IBD exhibited proapoptotic features. These data suggest the pathological involvement and the potential for therapeutic manipulation of these cells in patients with IBD.

Objectives: The optimal material for anterior chest wall reconstruction following chest wall resection remains controversial. The aim of this experimental study was to evaluate short-term, morphological and histological outcomes of anterior chest wall reconstruction with a rigid and bioabsorbable material in a canine model., Methods: Twenty adult beagle dogs underwent anterior chest wall resection. In the experimental group (n = 10), the anterior chest wall was reconstructed with a rigid and bioabsorbable material composed of poly-L-lactide acid matrix (60 wt%) and uncalcined and unsintered hydroxyapatite particles (40 wt%), whereas in the control group it was (n = 10) reconstructed with dual polypropylene mesh sheets. Short-term complication rates were compared with a χ(2) test. Postoperative sternal deviations were evaluated with sternal alignment angles using computed tomography and multiplanar reconstruction and were compared with Mann-Whitney U-test immediately after reconstruction, and at 1, 3, 6, 9 and 12 months postoperatively. Histological findings of the regenerated chest wall tissue were obtained after staining with haematoxylin and eosin and Elastica van Gieson (EVG) and compared at 3, 6, 9 and 12 months., Results: There was not a significant difference in the short-term postoperative complication rate (P = 0.53) and the complication rate was 20% (wound infection, n = 1 and lethal mediastinitis, n = 1) in the control group and 10% (wound infection, n = 1) in the experimental group. The postoperative sternal deviation was significantly less remarkable at 1 month (123.3 ± 32.2° vs 159.4 ± 19.7°, P = 0.027), 3 months (109.8 ± 34.7° vs 150.9 ± 34.2°, P = 0.039) and 12 months (61 ± 15.6° vs 170.3 ± 6.6°, P = 0.046) in the experimental group than in the control group, whereas no significant difference was noted immediately after reconstruction (165.7 ± 6.4° vs 168.4 ± 9.1°, P = 0.50). Histological findings showed dense connective tissue in the regenerated chest wall in both groups and showed chondroblasts in the regenerated chest wall tissue at 3 and 6 months only in the experimental group., Conclusions: Our results suggest that anterior chest wall reconstruction with a rigid and bioabsorbable material is feasible and may be a valuable alternative to reconstruction with a non-rigid and non-absorbable material., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Intrapleural adhesions following thoracotomy may be associated with prolonged operating time or a higher complication rate at reoperation. The aim of this experimental study was to investigate the anti-adhesion property of a bioabsorbable sheet following thoracotomy in a canine model., Methods: Ten adult beagle dogs underwent bilateral muscle-sparing thoracotomies with single ribs resected under general anaesthesia. A bioabsorbable sheet composed of poly-L-lactide copolymer (45 wt%) and ε-caprolactone (45 wt%) layered with polyglycolic acid (10 wt%) was sutured intrapleurally on the parietal pleura to cover the defect on the left, but not placed on the right side as a control. All the dogs were followed up with chest computed tomography until being sacrificed (6 months at the maximum). Thoracoscopic evaluations were performed at 1, 3 and 6 months for intrapleural adhesions at the thoracotomy site and absorption of the bioabsorbable sheet. The incidences of intrapleural adhesions were compared between the experimental side and the control side by the χ(2) test. Histological (macroscopic and microscopic) analyses of regenerated chest wall tissue were also performed at 1, 3 and 6 months., Results: All the dogs survived uneventfully until being sacrificed without any postoperative complications or significant radiological findings. The bioabsorbable sheet prevented intrapleural adhesions in all subjects. There were statistically significant differences in the incidence of intrapleural adhesions between the experimental side and the control side at the thoracotomy incision (0 vs 80%, P = 0.0014) at 1 month, (0 vs 66.7%, P = 0.014) at 3 months and (0 vs 75%, P = 0.028) at 6 months. The bioabsorbable sheet was found residual at 1, 3 and 6 months in all subjects. Histological analyses confirmed regenerated chest wall layers with significantly more capillary vessels at 1 month (P = 0.015), but not at 3 and 6 months (P = 0.84 and 0.41, respectively), in the regenerated mucosal and submucosal layers on the experimental side., Conclusions: Our findings suggest that the bioabsorbable sheet may prevent intrapleural adhesions with parietal pleurae regenerated with more vascularization at 1 month following thoracotomy. No adverse findings were noted with the sheet., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: We herein report on development of a composite (synthetic and biological) tracheal scaffold with vascularized autologous connective tissue in the omentum, followed by in situ tissue engineering of the composite scaffold with the pedicled omentum. In this preliminary report, we focus on development and evaluation of the vascularized autologous connective tissue in the omentum., Methods: In animal experiment 1, a polypropylene framework as a synthetic component was placed in the omental sac for 3 weeks and another was placed in the pouch of Douglas as a control in five beagle dogs. In animal experiment 2, a polypropylene framework placed in the omental sac for 3 weeks was compared with a polypropylene framework coated with porcine atelocollagen, which was also placed in the omental sac in another five dogs, to investigate whether the coating of porcine atelocollagen contributes to development of more vascularized connective tissue. Macroscopic, radiological and histological evaluations were performed for developed autologous connective tissue on the frameworks, with a focus on its thickness and capillary vessels., Results: In animal experiment 1, the polypropylene framework in the omentum developed a composite tracheal scaffold with homogeneous and significantly thicker (2.6 ± 0.5 vs 1.2 ± 0.4 mm, P <0.0001) connective tissue in which more capillary vessels per 10-power field of view (3.5 ± 2.2 vs 0 ± 0, P = 0.015) were identified, compared with the control in the pouch of Douglas. In animal experiment 2, the omentum developed significantly thicker connective tissue on the polypropylene framework coated with porcine atelocollagen (3.6 ± 0.7 vs 2.2 ± 0.4 mm, P <0.0001) in which not significantly more capillary vessels were identified (3.5 ± 2.2 vs 5.0 ± 2.7, P = 0.12), compared with the framework that was not coated., Conclusions: Placement of the polypropylene framework in the omental sac resulted in development of homogeneous and vascularized autologous connective tissue on the polypropylene framework for a composite tracheal scaffold. The framework coated with porcine atelocollagen did not show an additional benefit in inducing vascularization. This preliminary report will be followed by the long-term evaluations of in situ tissue engineering of the composite tracheal scaffold., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: There have been extensive studies regarding which types of T lymphocytes are involved in psoriasis vulgaris (PV). However, it has remained unclear which types of T lymphocytes might directly contribute to psoriasiform epidermal and vascular hyperplasia., Objectives: To understand the role of T-cell receptor (TCR)Vα24+ invariant natural killer (iNK)T cells in the development of PV., Methods: Seventeen patients were enrolled in this study. Using biopsy samples of PV plaques, TCRVα24(+) iNKT cells were investigated regarding their cytokine production to understand their roles in development of disease., Results: The number of interferon (IFN)-γ+ iNKT cells correlated with the length of the psoriasiform hyperplasia rete ridge and the Psoriasis Area and Severity Index. IFN-γ+ iNKT cells in psoriatic skin exhibited higher C-C chemokine receptor (CCR)5 expression, and the amount of C-C chemokine ligand (CCL)5, a ligand for CCR5, was increased in capillary veins of psoriasis plaques. CCR5+ iNKT-cell numbers significantly correlated with the number of capillary vein endothelial cells expressing CCL5 in PV. Furthermore, the number of CCL5+ capillary veins correlated with the maximum rete ridge length., Conclusions: IFN-γ/CCR5 expression in iNKT cells and CCL5 expression in vessels of dermal papillae correlate with the development of psoriasiform hyperplasia and microabscess. We propose that these iNKT cells may become useful targets for development of novel therapeutic approaches to PV., (© 2013 British Association of Dermatologists.)

IL-7R, FLT3, and CD43 are surface antigens expressed during the transition from pro-B to pre-B cells in BM. To understand interactions between their signaling pathways, we analyzed spontaneous mouse B-LBLs with dual MLV integration into Stat5a and Fiz1 or Stat5a and Hipk2. MLV integration resulted in up-regulation of these genes in lymphoma cells compared with normal pro-B cells from the BM. In lymphomas with both integrations into Stat5a and Fiz1, increases in phosphorylated STAT5A and expression of c-Myc, a target gene of STAT5A, were observed following stimulation of the FLT3. Clones with the dual integrations grew faster in IL-7 and FLT3L-supplemented medium than clones with Stat5a integration alone. On the other hand, in lymphomas with integrations into Stat5a and Hipk2, increases in phosphorylated STAT5A and expression of c-Myc were observed following cross-linking of CD43. In conclusion, FLT3 and CD43 signaling pathways involve STAT5A via Fiz1 and Hipk2 in B-LBLs. Identification of the dual MLV integration sites in B-LBLs, therefore, will provide an excellent tool for identification of the signaling pathways in B-LBLs.