PURPOSE: Cutaneous lymphocyte-associated antigen (CLA)-expressing CD8+T cells have been known to play an important role in the pathogenesis of atopic dermatitis (AD). However, the mechanisms underlying the loss of self-tolerance remain unclear. Regulatory T cells (Tregs) play a key role in the development of homeostasis in the immune system. We, therefore, hypothesized that a reduced ability of Tregs to inhibit autologous CD8+CLA+T cells might be underlying mechanism in AD. MATERIALS AND METHODS: CD8+CLA+T cells and Tregs were obtained from the peripheral blood of AD patients and control volunteers. The frequencies of CD8+CLA+T cells were evaluated. The proliferative responses of CD8+CLA+T cells were assessed by flow cytometry, and the levels of transforming growth factor-beta1 (TGF-beta1) and interleukin-10 (IL-10) in culture supernatants were detected by enzyme-linked immunosorbent assay. RESULTS: Our results revealed higher frequency and increased expression of perforin and granzyme-B in peripheral CD8+CLA+T cells in AD, and lower inhibitory ability of Tregs on proliferation of CD8+CLA+T cells in AD. Meanwhile, the levels of TGF-beta1 produced by Tregs were significantly lower in AD, and anti-TGF-beta1 abolished such suppression. CONCLUSION: The attenuated inhibitory ability of Tregs on hyper-activated autologous CD8+CLA+T cells, mediated by TGF-beta1, plays an important role in the pathogenesis of AD.
Adult ; Aged ; CD8-Positive T-Lymphocytes/drug effects/*immunology ; Case-Control Studies ; Cell Proliferation ; Cell Separation ; Dermatitis, Atopic/*immunology/pathology ; Female ; Granzymes/metabolism ; Humans ; Interleukin-10/metabolism ; Lymphocyte Count ; Male ; Perforin/metabolism ; Skin/*immunology/pathology ; T-Lymphocytes, Cytotoxic/drug effects/immunology ; T-Lymphocytes, Regulatory/drug effects/*immunology ; Transforming Growth Factor beta1/pharmacology

BACKGROUNDRenal hypertrophy has been regarded as the early feature of diabetic nephropathy (DN), which may eventually lead to proteinuria and renal fibrosis. However, the exact mechanism of renal hypertrophy is still unclear. The aim of this study was to investigate the possible association of connective tissue growth factor (CTGF) with renal hypertrophy in uninephrectomized diabetic rats.

METHODSSeventy-two Sprague-Dawley (SD) rats were randomly divided into two groups: control group (group C, n = 32) and diabetic nephropathy (group DN, n = 40). Each group was re-divided into 4 subgroups according to the experimental period. The rats were sacrificed at 1, 2, 4, and 8 weeks respectively after induction of diabetes. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) after rats had received uninephrectomy. Blood glucose (BG), body weight (BW), 24-h urinary albumin excretion (24hUalb), kidney weight (KW), KW/BW, glomerular tuft area (AG), glomerular tuft volume (VG), proximal tubular area (AT) at each time point, the width of glomerular basement membrane (GBM) and tubular basement membrane (TBM) at week 8 were measured when the rats were sacrificed. Renal expression of CTGF and p27kip1 were detected by immunohistochemical staining. The relationship between CTGF expression and increasing of VG and AT was analyzed.

RESULTSThere was a significant increase of 24hUalb, KW, and KW/BW from week 1 onward in diabetic rats compared to those in group C (P < 0.05, respectively), diabetic rats also had a significant increase of AG, VG, and AT from week 1 onward. It was also shown that diabetic rats had a thickening of GBM [(245.7 +/- 103.0) nm vs (121.8 +/- 19.1) nm, P < 0.01] and TBM [(767.7 +/- 331.1) nm vs (293.0 +/- 110.5) nm, P < 0.01] at week 8. There was a weak expression for CTGF and p27kip1 in normal glomeruli and tubuli, while a significant increasing expression of CTGF and p27kip1 was found in glomeruli and tubuli in diabetic kidney from week 1 onward (P < 0.05, respectively), and the extent of CTGF expression was positively correlated with AG (r = 0.92, P < 0.05), VG (r = 0.86, P < 0.05), AT (r = 0.94, P < 0.01) and positively correlated with the expression of p27kip1 (r = 0.96, P < 0.01).

CONCLUSIONThe expression of CTGF increases in diabetic rat kidney at the early stage, which might be an important mediator of renal hypertrophy through arresting cell cycling.

Albuminuria ; etiology ; Animals ; Connective Tissue Growth Factor ; Cyclin-Dependent Kinase Inhibitor p27 ; analysis ; Diabetes Mellitus, Experimental ; pathology ; Hypertrophy ; Immediate-Early Proteins ; analysis ; physiology ; Intercellular Signaling Peptides and Proteins ; analysis ; physiology ; Kidney ; pathology ; Male ; Nephrectomy ; Rats ; Rats, Sprague-Dawley ; Streptozocin

Angiotensin II Type 1 Receptor Blockers ; pharmacology ; Animals ; Biphenyl Compounds ; pharmacology ; Creatinine ; metabolism ; Diabetes Mellitus, Experimental ; metabolism ; pathology ; Hypertrophy ; Immunohistochemistry ; Kidney ; metabolism ; pathology ; Male ; Matrix Metalloproteinase 2 ; analysis ; genetics ; Rats ; Rats, Sprague-Dawley ; Streptozocin ; Tetrazoles ; pharmacology ; Tissue Inhibitor of Metalloproteinase-2 ; analysis ; genetics

Objective To measure the sagittal anatomical parameters of the spine and pelvis based on EOS imaging system, and to evaluate the stress of the lower lumbar spine by finite element analysis (FEA). Methods A total of 44 subjects examined by EOS imaging system were included, including 11 sacral lumbar vertebra patients and 33 normal subjects. The sagittal plane parameters of lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT) and sacral slope (SS) were measured and compared in both groups. Pearson test was used to analyze the correlation between PI and LL in the two groups. At the same time, the finite element model of the lower lumbar vertebra was established. The stress condition of the lumbar spine model during forward bending, backward extension and left and right bending was evaluated by FEA method. Results The differences of PI, PT, SS and LL between the two groups were statistically significant (P<0.05). The correlation study found that there was a positive correlation between the two groups of subjects' PI and LL, including the lumbarization group (r = 0.69, P<0.05) and the normal group (r = 0.52, P<0.05). Under the conditions of forward bending, backward stretching, left bending and right bending, the bending moment of the model was 2 Nmm, and the stress concentration gradually decreased from bottom to top. The maximum stress concentration point was located at the lower articular process. Conclusion The physiological curvature and stress distribution of the lumbar spine in lumbarization population were different than normal, especially the stress concentration of the transitional intervertebral disc and articular process joint was obvious, and early degeneration of the spine was easy to occur.