Peripheral blood T lymphocytosis in thymoma: an insight into immunobiology
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
Authors: Mishra, Shruti; Padhi, Somanath; Adhya, Amit Kumar; DasMajumdar, Saroj Kumar; Pattnaik, Ashutosh; Chhabra, Gaurav
Abstract
Purpose Peripheral blood T lymphocytosis (PBTL) is a rare, yet poorly understood manifestations of thymoma, which is postulated to be linked with autoimmune/paraneoplastic manifestations such as myasthenia gravis (MG), pure red cell aplasia (PRCA), etc.; more commonly encountered in this neoplasm. Method We aim to describe the flowcytometric immunophenotypic data of PBTL in a 43-year-old male; 6 months after successful completion of chemoradiotherapy (CT/RT) for a large, invasive, and metastatic type B1 thymoma; and present a comprehensive review of all such cases reported over last 42 years (N = 21) (1977-2019). Result A larger size of the tumors (>= 10 cm), presence of local invasion and/or distant metastasis, and type B (cortical or lymphocyte rich) histology were more likely to be associated with PBTL. Tumors associated with MG/PRCA (N = 9/21) tend to have lower PBTL compared to those without such manifestations; and PBTL subsided following thymectomy with or without CT/RT. Immunophenotypic analysis of PB revealed a CD8 + > CD4 + mature (naive) polyclonal T cells resembling late cortical thymocytes. Conclusion Thymic intratumoral microenvironment might influence occurrence PBTL that may have a pathophysiologic link to development of autoimmune manifestations. Immunophenotypic characteristics of peripheral blood lymphoid cells should be the clue for accurate characterization and to avoid a misdiagnosis of a lymphoproliferative neoplasm.
Leonurine Regulates Treg/Th17 Balance to Attenuate Rheumatoid Arthritis Through Inhibition of TAZ Expression
FRONTIERS IN IMMUNOLOGY
Authors: Du, Yan-Yi; Chen, Zhi-Xin; Liu, Min-Ying; Liu, Qing-Ping; Lin, Chang-Song; Chu, Cong-Qiu; Xu, Qiang
Abstract
Leonurine, an active alkaloid extracted fromHerba leonuri, is reported to have potent anti-inflammatory activity against rheumatoid arthritis (RA). However, the molecular mechanism of action of leonurine in RA remains poorly understood. In this study, we detected 3,425 mRNAs differentially expressed between CD4(+)T cells of RA patients and those of healthy individuals using microarray raw data mining. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that transcriptional coactivator with PDZ-binding motif (TAZ) regulates a variety of biological processes including T-helper (Th)-17 cell development, and was thus selected for functional verification. In a naive CD4(+)T cell differentiation assay, we found that TAZ overexpression was associated with impaired balance between T regulatory (Treg) and Th17 cellsin vitro. TAZ overexpression increased the levels of the pro-inflammatory cytokines interleukin (IL)-17, IL-1 beta, and tumor necrosis factor (TNF)-alpha and decreased that of the anti-inflammatory cytokine IL-10. Leonurine treatment had a direct recovery effect on the impaired balance and reduced the expression of TAZ and led to normalization of IL-17, IL-1 beta, and TNF-alpha and IL-10. Furthermore, IL-6 was found to promote the expression of TAZ and receptor activator of nuclear factor kappa-B ligand (RANKL), and RANK. Leonurine significantly inhibited TAZ-mediated expression of RANKL, and RANK and IL-6 in synovial fibroblasts. We conclude that the therapeutic effect of leonurine was through suppression of TAZ led to restoration of Treg/Th17 balance and suppression of synovial fibroblast action.