Xichuan Yang

Increased circulating follicular helper T cells and activated B cells correlate with disease severity in patients with psoriasis

Follicular Helper T (TFH) Cells are a population of recently discovered CD4+ T cells involved in autoimmune diseases. However, the contribution of TFH cells in patients with psoriasis remains unknown.

Single-nucleotide Polymorphism and Haplotypes of TNIP1 Associated with Systemic Lupus Erythematosus in a Chinese Han Population

Objective. To determine the association of systemic lupus erythematosus (SLE) with single-nucleotide polymorphisms (SNP) in the TNIP1 gene and compare the expression of this gene in cases and controls from a Chinese Han population in this replication study. Methods. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry was used to genotype 19 SNP in TNIP1 in Chinese Han patients with SLE (n = 341) and controls (n = 356). Genotypes were analyzed by codominant, dominant, and recessive models. Analysis of allele frequencies and linkage disequilibrium was also performed. Western blotting and qRT-PCR were used to measure the expression of these genes in peripheral blood mononuclear cells of SLE cases and controls. Results. Seven SNP loci were significantly associated with SLE in our population (p < 0.05 for all comparisons). Two TNIP1 gene haplotypes (ATTGCGC and GTCCTAT) were associated with SLE (p = 0.0246 and p = 0.0024, respectively). Western blotting and qRT-PCR results provide evidence that patients with SLE had significantly reduced expression of TNIP1/ABIN-1 relative to controls. Conclusion. Analysis of SNP in the TNIP1 gene and expression of this gene in peripheral blood lymphocytes indicated these SNP were associated with the occurrence of SLE in Han Chinese patients. Future studies should examine the roles of these SNP in the pathogenesis of SLE.

Recurrent generalized indeterminate cell histiocytosis: A case report

To the Editor: Indeterminate cell histiocytosis (ICH) is a rare disease that is clinically characterized by multiple asymptomatic red, yellow, or reddish brown papules and nodules that arise in otherwise healthy individuals. Here we report a patient with recurrent generalized ICH. A 30-year-old woman had a 2-year history of disseminated multiple skin-colored, red, or reddishbrown nodules. The lesions varied in diameter from 1 to 4 cm and were initially occasionally mildly pruritic and painful. The lesions spontaneously disappeared over the course of 12 months without any treatment, leaving hyperpigmented macules. Three months later, the patient experienced a recurrence of the lesions that spread from the lower limbs to the remainder of thebody.Her mucousmembraneswere not involved, and the patient was otherwise asymptomatic (Fig 1). Routine laboratory studies were within normal limits. A computed tomographic scan of her head, a chest radiograph, and an abdominal sonographic scan showed no abnormalities. The histopathologic examination revealed a diffuse, monomorphus, nonepidermotropic infiltrate of

Association of CD8(+) T lymphocyte repertoire spreading with the severity of DRESS syndrome

T-cell receptor (TCR)-mediated cross-recognition is a major mechanism in the pathogenesis of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. However, the characteristics of the TCR repertoire and the clinical significance of repertoire reformation throughout the course of DRESS are unknown. Here, we isolated CD4+ and CD8+ T-cells from peripheral blood of 8 DRESS patients at 10-day intervals and, sequenced CDR3-regions of the TCRB chain by high-throughput sequencing to analyze the dynamic reformation in the T-cell repertoire hierarchy. Compared with healthy donors, T-cell expanded in peripheral repertoires from DRESS patient. The extent of fluctuation of dominant CD8+ T-cell clones, but not of CD4+ counterparts, correlated positively with the clinical severity and helped classify the enrolled subjects into “fluctuant” and “flat” repertoire groups. The anti-herpesvirus response, which was measured using anti-EBV/HHV antibodies, and the proportion of the homologous CD8+ EBV-specific clonotypes, in the “fluctuant” group was substantial higher than that in the “flat” group. Furthermore, autoimmune sequelae were observed in a cured “fluctuant” patient. Collectively, the clinical relevance of the fluctuant CD8+ T-cell repertoires supports the notion that herpes virus-mediated continuously de novo priming of newly pathogenic CD8+ T-cell clones is an alternate mechanism responsible for the pathogenicity of DRESS.

c-Jun N-terminal kinase (JNK)-phospho-c-JUN (ser63/73) pathway is essential for FOXP3 nuclear translocation in psoriasis

BACKGROUND In some psoriatic patients, impaired function of FOXP3+ regulatory T cells has been identified without well-uncovered mechanism(s). Meanwhile, dysregulation of FOXP3 nuclear translocation has been observed in some autoimmune syndromes and in some cancer cells. OBJECTIVE To investigate whether there is dysregulation of FOXP3 nuclear translocation in some psoriatic patients and to explore the signal pathway responsible for FOXP3 nuclear translocation. METHODS CD4+CD25+ T cells were purified from peripheral blood mononuclear cells by magnetic-bead-based method. FOXP3 expression pattern in psoriasis was analyzed by immunohistochemical staining. Transient and stable cell lines were established by exogenous construct transfection and retrovirus infection respectively. Cytoplasmic and nuclear FOXP3 was analyzed by immunoprecipitation, western blot and immunofluorescence. RESULTS We observed that some psoriatic patients showed cytoplasmic retention of FOXP3 and these patients had higher serum IL-17 and disease severity. We found that c-Jun N-terminal kinase (JNK) was essential to FOXP3 nuclear translocation. Inhibition of JNK pathway caused cytoplasmic retention of FOXP3. This inhibition could also impair the promotion of FOXP3 nuclear translocation by UVB. Next we found that phospho-c-JUN (ser63/73), main downstream of JNK pathway, could interact with FOXP3 and promoted FOXP3 nuclear translocation. CONCLUSION Our study demonstrated that JNK-phospho-c-JUN (ser63/73) pathway was essential for FOXP3 nuclear translocation in psoriasis. Our study suggested selective manipulation of JNK in Tregs seems to be a promising choice for the development of drugs in the treatment of autoimmune inflammatory diseases.

Neutrophil elastase promotes proliferation of HaCaT cell line and transwell psoriasis organ culture model.

Background  Neutrophil elastase (NE) plays an important role in psoriasis. In this study we observed the effect of NE on the proliferation of HaCaT cells and transwell psoriasis organ culture model and investigated the mechanism.

Pharmacology and therapeutics: Neutrophil elastase promotes proliferation of HaCaT cell line and transwell psoriasis organ culture model

Background  Neutrophil elastase (NE) plays an important role in psoriasis. In this study we observed the effect of NE on the proliferation of HaCaT cells and transwell psoriasis organ culture model and investigated the mechanism.

HPV16E7 tumor antigen modified by KDEL sequence induce specific cytotoxic T lymphocytes-dependent antitumor immunity

BACKGROUND Infection by high-risk HPV (human papillomavirus) is the primary cause of cervical cancer. Dendritic cell-based (DC-based) therapeutic vaccine represents a promising approach to the prevention and treatment of many cancers, including HPV-related cancers, but current strategies have met with only limited success in preclinical and clinical research. It is necessary to find a properly and effective antigen presenting system of DC-based vaccine. OBJECTIVE To design a new HPV16 therapeutic vaccine using an endoplasmic reticulum (ER) retrieval signal and study its ability to induce the specific CTL activity in vitro and in vivo. METHODS E7(p)-KDEL and its control peptide were synthesized on solid phase. A series of methods were used, including standard (51)Cr-labeled release assay, enzyme-linked immunospot (ELISPOT) assay and ELISA, to detect the CTL activity induced by different peptides. Prophylactic models and therapeutic models were examined to detect the in vivo effectiveness of E7(p)-KDEL-loaded DCs. RESULTS The specific CTL activity induced by E7(p)-KDEL-loaded DCs was much stronger than that induced by the other peptide-loaded DCs. Comparing with the control peptides, after incubation with the spleen cells of mice, the E7(p)-KDEL-loaded DCs could induce higher concentration of secreted IFN-gamma and had higher ELISPOT numbers. In animal models, E7(p)-KDEL-loaded DCs vaccines effectively protected mice against fatal TC-1 tumor challenge and cured tumor-bearing mice. CONCLUSIONS The ER retrieval signal-mediated antigen delivery system may have important clinical application for cancer therapy, even virus infectious disease and autoimmune disease.

The umbilical polyp: a report of two cases and literature review

A 17-year-old girl presented with an unusual protuberant appearance of the umbilicus since birth. This lesion produced serous discharge that sometimes stuck to her clothes. The patient had been seen in early childhood, but had not received any therapy. Physical examination showed a 0.5 × 0.5-cm, well-defined, rounded, polypoid lesion in the umbilicus. This lesion was red and moist, and produced serous secretions (Fig. 1). The hair, nails, and mucous membranes of the patient were normal. Systemic examination revealed no other abnormalities. The preand postnatal history of the patient were unremarkable, and there was no family history of congenital anomalies. A review of the patient’s laboratory investigations showed normal blood cell counts, liver function tests, and serum electrolytes. A radiograph of the abdomen was normal. Because of these unusual features, a biopsy of the lesion was

Congenital localized basaloid follicular hamartoma: a case report and review of the literature

Basaloid follicular hamartoma (BFH) is a rare benign follicular hamartoma, with variable clinical features. Histopathologically, it is likely to be confused with basal cell carcinoma (BCC). BFH may be present alone or along with hereditary skin diseases, such as Bazex-DupreChristol syndrome, Brown-Crounse syndrome, myasthenia gravis, alopecia, and systemic lupus erythematosus. Here we report a case of congenital localized BFH.