Serum and blister fluid levels of cytokines and chemokines in pemphigus and bullous pemphigoid

Bullous pemphigoid and pemphigus constitute two major autoimmune blistering diseases (AIBD) with complicated disease pathomechanisms involving a multitude of cytokines and immunological pathways. The purpose of our literature review of the cytokines and chemokines involved in these AIBDs was to allow for a meta-analysis of studies detailing differential cytokine and chemokine changes in these conditions. Elucidation of inflammatory pathways could lead to more targeted therapies, several of which specific monoclonal antibodies already exist and are used safely for other autoimmune diseases. A systematic review of the Pubmed/Medline database was performed for articles characterizing cytokines/chemokines involved in BP and pemphigus. Further, a meta-analysis was carried out using standardized methods, including assessment for heterogeneity. The results of our analysis demonstrated numerous inflammatory alterations in these AIBDs. Significant alterations included serum levels of IL-5, IL-6, IL-8, IL-17, CCL-17, and CCL-26 in patients with BP, and increased blister fluids levels of IL-5, IL-6, IL-8, CCL11, and TNF-α. Blister fluid levels of IL-1α are decreased in BP. In pemphigus, we identified significantly increased serum levels of IL-10, IL-17, and CCL17. We have additionally summarized all studies excluded from meta-analysis to provide a comprehensive summary of cytokine/chemokine alterations in these two conditions.     

Statins can suppress DC‐mediated Th2 responses through the repression of OX40‐ligand and CCL17 expression

DCs and epithelial cell‐derived thymic stromal lymphopoietin (TSLP) have pivotal roles in allergic inflammation. TSLP stimulates myeloid DCs to express OX40‐ligand (OX40L) and CCL17, which trigger and maintain Th2 cell responses. We have previously shown that statins, which are HMG‐CoA reductase inhibitors, have the ability to suppress type I IFN production by plasmacytoid DCs. Here, we extended our previous work to examine the immunomodulatory effect of statins on allergic responses, particularly the TSLP‐dependent Th2 pathway induced by myeloid DCs. We found that treatment of TSLP‐stimulated DCs with either pitavastatin or simvastatin suppressed both the DC‐mediated inflammatory Th2 cell differentiation and CRTH2⁺CD4⁺ memory Th2 cell expansion and also repressed the expressions of OX40L and CCL17 by DCs. These inhibitory effects of statins were mimicked by treatment with either a geranylgeranyl‐transferase inhibitor or Rho‐kinase inhibitor and were counteracted by the addition of mevalonate, suggesting that statins induce geranylgeranylated Rho inactivation through a mevalonate‐dependent pathway. We also found that statins inhibited the expressions of phosphorylated STA6 and NF‐κB‐p50 in TSLP‐stimulated DCs. This study identified a specific ability of statins to control DC‐mediated Th2 responses, suggesting their therapeutic potential for treating allergic diseases.     

TSLP Expression and High Serum TSLP Level Indicate a Poor Prognosis in Gastric Cancer Patients

Background

Thymic stromal lymphopoietin (TSLP) plays an important role in promoting tumor survival, by manipulating the immune response and angiogenesis. However, the clinical significance of TSLP in gastric cancer is unclear.

Methods

Immunohistochemistry was used to investigate TSLP expression in non-cancerous gastric mucosa and gastric cancer tissue from patients with gastric cancer. Serum TSLP levels were measured using an enzyme-linked immunosorbent assay.

Results

Tumors with TSLP expression were significantly larger than those without TSLP expression. TSLP expression was observed more frequently in advanced (T2/T3/T4) than in early (T1) gastric cancer and in stage 3/4 than in stage 1/2. Lymph node metastasis, liver metastasis, positive peritoneal lavage cytology, lymphatic invasion, and vascular invasion occurred significantly more often in TSLP-expressing than in non-expressing tumors. The prognosis of patients with TSLP-positive tumors was significantly worse than that of patients with TSLP-negative tumors. Patients with high serum TSLP concentrations also had a significantly worse prognosis than those with low concentrations. Multivariate analysis identified serum TSLP level as an independent prognostic indicator.

Conclusion

TSLP is closely related to the progression of gastric cancer and may predict survival in these patients.     

感染斯氏狸殖吸虫大鼠IL-4、IL-6、TSLP、TGF-β1水平检测

目的研究斯氏狸殖吸虫感染引起的SD大鼠Th2免疫反应产生的细胞因子IL-4、IL-6、TSLP、TGF-β1水平,探寻寄生虫感染所致大鼠细胞免疫反应情况。方法用斯氏狸殖吸虫囊蚴感染SD大鼠5只,于感染后16周对其血清进行IL-4、IL-6、TSLP、TGF-β1的ELISA检测。结果 IL-4、TSLP、TGF-β1无显著变化,分别为0.34 pg/ml、8.69 pg/ml、2 06681.86 pg/ml(P0.05),IL-6显著升高到40.45 pg/ml,具有统计学意义(P0.05)。结论感染SD大鼠Th2免疫反应活化,IL-6表达显著上调。     

TSLP在肺癌组织中的表达及其与调节性T 细胞的相关性*

目的:探讨胸腺基质淋巴生成素（thymic stromal lymphopoietin ,TSLP）在肺癌组织中的表达及其与临床指标以及局部调节性T 细胞（Regulatory T cells,Tregs）数量的相关性。方法:分别采用Q-RT-PCR 和免疫组织化学染色方法检测TSLP在不同病变类型的肺组织中的表达,分析TSLP在不同病变肺组织中的表达差异;并运用免疫组化方法检测TSLP蛋白在不同病理类型的肺癌组织中的表达,分析TSLP表达与临床病理特征之间的相关性;采用免疫组化法检测肺癌组织中的Tregs细胞,分析TSLP表达与肿瘤局部Tregs细胞数量之间的关系。结果:TSLP基因在肺癌组织、癌旁组织、非肿瘤肺上皮均表达阳性,且表达差异无统计学意义;TSLP蛋白表达于胞浆中,其在肺癌组织中的阳性表达率（69.57%）显著高于肺的良性病变（13.33%）和非肿瘤肺上皮（30.00%）,且TSLP表达与肿瘤大小和淋巴结转移有关;TSLP表达阳性的患者其肿瘤局部浸润的调节性T 细胞数量明显高于TSLP阴性组（P<0.05）。 结论:TSLP蛋白在肺癌组织中表达增加,且与肿瘤局部调节性T 细胞数量增多有关,这提示TSLP可能是通过诱导Tregs增加在肺癌免疫耐受中发挥作用。