CD53, a suppressor of inflammatory cytokine production, is associated with population asthma risk via the functional promoter polymorphism-1560 C > T
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
Authors: Lee, Haeyong; Bae, Sungmin; Jang, Jaewoong; Choi, Byoung Whui; Park, Choon-Sik; Park, Jong Sook; Lee, Seung-Hyo; Yoon, Yoosik
Abstract
Background: In this study, the association of asthma with CD53, a member of the tetraspanin family, was assessed for the first time in a mechanism-based study. Methods: Genetic polymorphisms of CD53 were analyzed in 591 subjects and confirmed in a replication study of 1001 subjects. CD53 mRNA and protein levels were measured in peripheral blood leukocytes, and the effects of the promoter polymorphisms on nuclear factor binding were examined by electrophoretic mobility shift assay. Cellular functional studies were conducted by siRNA transfections. Results: Among tagging SNPs of CD53, the - 1560 C>T in the promoter region was significantly associated with asthma risk. Compared with the CC genotype, the CT and IT genotypes were associated with a higher asthma risk, with odd ratios of 1.74 (P=0.009) and 2.03 (P=0.004), respectively. These findings were confirmed in the replication study with odd ratios of 1.355 (P=0.047) and 1.495 (P=0.039), respectively. The - 1560 C>T promoter SNP had functional effects on nuclear protein binding as well as mRNA and protein expression levels in peripheral blood leukocytes. When CD53 was knocked down by siRNA in THP-1 human monocytic cells stimulated with house dust mite, the production of inflammatory cytokines as well as NF kappa B activity was significantly over-activated, suggesting that CD53 suppresses over-activation of inflammatory responses. Conclusions: The - 1560 C>T SNP is a functional promoter polymorphism that is significantly associated with population asthma risk, and is thought to act by directly modulating nuclear protein binding, thereby altering the expression of CD53, a suppressor of inflammatory cytokine production. (C) 2013 Elsevier B.V. All rights reserved.
Multispectral imaging reveals the tissue distribution of tetraspanins in human lymphoid organs
HISTOCHEMISTRY AND CELL BIOLOGY
Authors: de Winde, Charlotte M.; Zuidscherwoude, Malou; Vasaturo, Angela; van der Schaaf, Alie; Figdor, Carl G.; van Spriel, Annemiek B.
Abstract
Multispectral imaging is a novel microscopy technique that combines imaging with spectroscopy to obtain both quantitative expression data and tissue distribution of different cellular markers. Tetraspanins CD37 and CD53 are four-transmembrane proteins involved in cellular and humoral immune responses. However, comprehensive immunohistochemical analyses of CD37 and CD53 in human lymphoid organs have not been performed so far. We investigated CD37 and CD53 protein expression on primary human immune cell subsets in blood and in primary and secondary lymphoid organs. Both tetraspanins were prominently expressed on antigen-presenting cells, with highest expression of CD37 on B lymphocytes. Analysis of subcellular distribution showed presence of both tetraspanins on the plasma membrane and on endosomes. In addition, CD53 was also present on lysosomes. Quantitative analysis of expression and localization of CD37 and CD53 on lymphocytes within lymphoid tissues by multispectral imaging revealed high expression of both tetraspanins on CD20(+) cells in B cell follicles in human spleen and appendix. CD3(+) T cells within splenic T cell zones expressed lower levels of CD37 and CD53 compared to T cells in the red pulp of human spleen. B cells in human bone marrow highly expressed CD37, whereas the expression of CD53 was low. In conclusion, we demonstrate differential expression of CD37 and CD53 on primary human immune cells, their subcellular localization and their quantitative distribution in human lymphoid organs. This study provides a solid basis for better insight into the function of tetraspanins in the human immune response.