The thymus provides the essential microenvironment for T-cell development and maturation. Thymic epithelial cells （TECs）, which are composed of thymic cortical epithelial cells （cTECs） and thymic medullary epithel...The thymus provides the essential microenvironment for T-cell development and maturation. Thymic epithelial cells （TECs）, which are composed of thymic cortical epithelial cells （cTECs） and thymic medullary epithelial cells （mTECs）, have been well documented to be critical for these tightly regulated processes. It has long been controversial whether the common progenitor cells of TECs could give rise to both cTECs and mTECs. Great progress has been made to characterize the common TEC progenitor cells in recent years. We herein discuss the sole origin paradigm with regard to TEC differentiation as well as these progenitor cells in thymus regeneration.展开更多
Mouse thymic stromal cell line 4 (MTSC4) is one of the stromal cell lines established in our laboratory. While losing the characteristics of epithelial cells, they express some surface markers shared with thymic dendr...Mouse thymic stromal cell line 4 (MTSC4) is one of the stromal cell lines established in our laboratory. While losing the characteristics of epithelial cells, they express some surface markers shared with thymic dendritic cells (TDCs). To further study the biological functions of these cells, we compared the capability of MTSC4 with TDCs in the induction of thymocyte apoptosis, using thymic reaggregation culture system. Apoptosis of thymocytes induced by MTSC4 and TDCs was measured by Annexin V and PI staining and analyzed by flow cytometry. We found that MTSC4 selectively augmented the apoptosis of CD4^+8^+ (DP) thymocytes. This effect was Fas/FasL independent and could not be blocked by antibodies to MHC class Ⅰ and class Ⅱ molecules. In addition, MTSC4 enhanced the apoptosis of DP thymocytes from different strains of mice, which implies that MTSC4-induced thymocyte apoptosis is not mediated by the TCR recognition of self peptide/MHC molecules. In contrast to MTSC4, thymocyte apoptosis induced by TDCs was MHC-restricted. Thus, MHC-independent fashion of stromal-DP thymocyte interaction may be one of the ways to induce thymocyte apoptosis in thymus. Our study has also shown that the interaction of MTSC4 stromal cells and thymocytes is required for the induction of thymocyte apoptosis.展开更多
Supernatants from human primary thymic epithelial cell culture were collected. The proliferationpromoting effect of the supernatant on mouse thymocyte, as well as on Tcell line 85, Be 13, HDMar, Peer, Loucy, Molt4, R...Supernatants from human primary thymic epithelial cell culture were collected. The proliferationpromoting effect of the supernatant on mouse thymocyte, as well as on Tcell line 85, Be 13, HDMar, Peer, Loucy, Molt4, Reh and Jurkat, were observed. The results demonstrated that the supernatants could increase spontaneous 3 HTdR intake of mouse thymocyte, promote ConAinduced thymocyte proliferation and stimulate the proliferation of 85 cell or the cells of HDMar, Loucy and Jurkat at stationary phase, but did not display any effect on Be13, Peer, Molt4 and Reh cells.展开更多
The effect of thymic stromal lymphopoietin（TSLP） on macrophage-derived foam cell formation and the underlying mechanism were studied. Macrophages isolated from C57BL/6 mice were co-cultured in vitro with different c...The effect of thymic stromal lymphopoietin（TSLP） on macrophage-derived foam cell formation and the underlying mechanism were studied. Macrophages isolated from C57BL/6 mice were co-cultured in vitro with different concentrations of TSLP or TSLPR-antibody in the presence of oxidized low density lipoprotein（ox-LDL）. The effects of TSLP on macrophage-derived foam cell formation were observed by using oil red O staining and intracellular lipid determination. The expression levels of foam cell scavenger receptors（CD36 and SRA） as well as ABCA1 and TSLPR were detected by using RT-PCR and Western blotting. As compared with the control group, TSLP treatment significantly promoted lipid accumulation in macrophages, significantly increased protein expression of CD36 and TSLPR in a dose-dependent manner, and significantly reduced the expression of ABCA1 protein in a dose-dependent manner. No significant differences were noted between the TSLPR-antibody group and the control group. TSLP may down-regulate the expression of cholesterol efflux receptor ABCA1 and up-regulate scavenger receptor expression via the TSLPR signaling pathway, thereby promoting macrophage-derived foam cell formation.展开更多
The MTEC1 cell line, established in our laboratory, is a normal epithelial cell line derived from thymus medulla of Balb/c mice and these cells constitutively produce multiple cytokines. The selection of thymic microe...The MTEC1 cell line, established in our laboratory, is a normal epithelial cell line derived from thymus medulla of Balb/c mice and these cells constitutively produce multiple cytokines. The selection of thymic microenvironment on developing T cells was investigated in an in vitro system. Un-separated fresh thymocytes from Balb/c mice were cocul-tured with MTECl cells or/and MTEC1-SN,then,the viability, proliferation and phenotypes of cultured thymocytes were assessed. Without any exogenous stimulus, both MTECl cells and MTECl -SN were able to maintain the viability of thymocytes, while only the MTECl cells, not the MTECl -SN, could directly activate thymocytes to exhibit moderate proliferation, indicating that the proliferative signal is delivered through cell surface interactions of MTECl cells and thymocytes. Phenotype analysis on FACS of viable thymocytes after coculture revealed that MTECl cells preferentially activate the subsets of CD4+ CDS', CD4+ CD8+ and CD4- CD8- thymocytes; whereas MTEC1- SN preferentially maintained the viability of CD4+ CD8- and CD4-CD8+ thymocyte subsets.For the Con A-activated thymocytes, both MTEC1 cells and MTEC1-SN provided accessory signal(s) to significantly increase the number of viable cells and to markedly enhance the proliferation of thymocytes with virtually equal potency, phenotyped as CD4+CD8-, CD4-CD8+, and CD4- CD8- subsets. In summary, MTEC1 cells displayedselective support to the different thymocyte subsets , and the selectivity is dependent on the status of thymocytes.展开更多
Thymic epithelial tumors(TETs) are uncommon neoplasms with a wide range of anatomical, clinical, histological and molecular malignant entities. To date the management of TETs within clinical practice is based on a mul...Thymic epithelial tumors(TETs) are uncommon neoplasms with a wide range of anatomical, clinical, histological and molecular malignant entities. To date the management of TETs within clinical practice is based on a multimodal therapeutic strategy including surgery, chemotherapy and radiotherapy with a multidisciplinary approach and prognostic evaluation is mainly based on Masaoka staging and World Health Organization classification. Therefore novel strategies are needed, especially for refractory and/or recurrent TETs and for thymic carcinomas that present a poor prognosis. Personalized approaches are currely being developed and molecular targets are emerging from recent integrated genomic analyses. Targeted therapy will represent an important treatment option for TETs with an aggressive histology. To date, data indicate that vascular endothelial growth factor molecules, insulinlike growth factor 1 receptor, cyclin-dependent kinases and mammalian target of rapamycin may be potentially useful as targeted biological therapies.展开更多
It has been reported that atopic dermatitis (AD) and ulcerative colitis are related. However, the mechanism underlying this association has not been clarified. We therefore explored how AD induces ulcerative colitis. ...It has been reported that atopic dermatitis (AD) and ulcerative colitis are related. However, the mechanism underlying this association has not been clarified. We therefore explored how AD induces ulcerative colitis. We developed an AD mouse model (NC/Nga mice) with ulcerative colitis by administering dextran sodium sulfate (DSS) for five days. DSS-induced ulcerative colitis was deteriorated in our conventional AD mouse model compared with specific-pathogen-free (SPF) mice. The plasma levels of thymic stromal lymphopoietin (TSLP) and tumor necrosis factor-α increased the most in DSS-treated conventional mice. Furthermore, the expression of dendritic cells (DC), retinoid-related orphan receptor (ROR)γt (marker of T helper 17 cells [Th17]), interleukin (IL)-17, GATA binding protein 3 (GATA3) (marker of Th2), and IL-4 increased the most in the colon of the DSS-treated conventional mice compared with DSS-treated SPF mice. In addition, TSLP inhibitor (TSLP neutralizing antibody) did not exacerbate ulcerative colitis in DSS-treated conventional mice. These results indicate that TSLP/DC/Th2 and Th17 play major roles in the exacerbation of ulcerative colitis by AD.展开更多
文摘The thymus provides the essential microenvironment for T-cell development and maturation. Thymic epithelial cells （TECs）, which are composed of thymic cortical epithelial cells （cTECs） and thymic medullary epithelial cells （mTECs）, have been well documented to be critical for these tightly regulated processes. It has long been controversial whether the common progenitor cells of TECs could give rise to both cTECs and mTECs. Great progress has been made to characterize the common TEC progenitor cells in recent years. We herein discuss the sole origin paradigm with regard to TEC differentiation as well as these progenitor cells in thymus regeneration.
基金This work was funded by grants from Major State Bascic Research Development Program of China(No.G1999053904)National Natural Science Foundation of China(No.30271200)Young Scentist Cooperation Research Fund(No.39928019).
文摘Mouse thymic stromal cell line 4 (MTSC4) is one of the stromal cell lines established in our laboratory. While losing the characteristics of epithelial cells, they express some surface markers shared with thymic dendritic cells (TDCs). To further study the biological functions of these cells, we compared the capability of MTSC4 with TDCs in the induction of thymocyte apoptosis, using thymic reaggregation culture system. Apoptosis of thymocytes induced by MTSC4 and TDCs was measured by Annexin V and PI staining and analyzed by flow cytometry. We found that MTSC4 selectively augmented the apoptosis of CD4^+8^+ (DP) thymocytes. This effect was Fas/FasL independent and could not be blocked by antibodies to MHC class Ⅰ and class Ⅱ molecules. In addition, MTSC4 enhanced the apoptosis of DP thymocytes from different strains of mice, which implies that MTSC4-induced thymocyte apoptosis is not mediated by the TCR recognition of self peptide/MHC molecules. In contrast to MTSC4, thymocyte apoptosis induced by TDCs was MHC-restricted. Thus, MHC-independent fashion of stromal-DP thymocyte interaction may be one of the ways to induce thymocyte apoptosis in thymus. Our study has also shown that the interaction of MTSC4 stromal cells and thymocytes is required for the induction of thymocyte apoptosis.
文摘Supernatants from human primary thymic epithelial cell culture were collected. The proliferationpromoting effect of the supernatant on mouse thymocyte, as well as on Tcell line 85, Be 13, HDMar, Peer, Loucy, Molt4, Reh and Jurkat, were observed. The results demonstrated that the supernatants could increase spontaneous 3 HTdR intake of mouse thymocyte, promote ConAinduced thymocyte proliferation and stimulate the proliferation of 85 cell or the cells of HDMar, Loucy and Jurkat at stationary phase, but did not display any effect on Be13, Peer, Molt4 and Reh cells.
基金supported by the National Natural Science Foundation of China(No.81170258)
文摘The effect of thymic stromal lymphopoietin（TSLP） on macrophage-derived foam cell formation and the underlying mechanism were studied. Macrophages isolated from C57BL/6 mice were co-cultured in vitro with different concentrations of TSLP or TSLPR-antibody in the presence of oxidized low density lipoprotein（ox-LDL）. The effects of TSLP on macrophage-derived foam cell formation were observed by using oil red O staining and intracellular lipid determination. The expression levels of foam cell scavenger receptors（CD36 and SRA） as well as ABCA1 and TSLPR were detected by using RT-PCR and Western blotting. As compared with the control group, TSLP treatment significantly promoted lipid accumulation in macrophages, significantly increased protein expression of CD36 and TSLPR in a dose-dependent manner, and significantly reduced the expression of ABCA1 protein in a dose-dependent manner. No significant differences were noted between the TSLPR-antibody group and the control group. TSLP may down-regulate the expression of cholesterol efflux receptor ABCA1 and up-regulate scavenger receptor expression via the TSLPR signaling pathway, thereby promoting macrophage-derived foam cell formation.
基金grants from the China medical board, USA,and from the national foundation of natural scirnces,China
文摘The MTEC1 cell line, established in our laboratory, is a normal epithelial cell line derived from thymus medulla of Balb/c mice and these cells constitutively produce multiple cytokines. The selection of thymic microenvironment on developing T cells was investigated in an in vitro system. Un-separated fresh thymocytes from Balb/c mice were cocul-tured with MTECl cells or/and MTEC1-SN,then,the viability, proliferation and phenotypes of cultured thymocytes were assessed. Without any exogenous stimulus, both MTECl cells and MTECl -SN were able to maintain the viability of thymocytes, while only the MTECl cells, not the MTECl -SN, could directly activate thymocytes to exhibit moderate proliferation, indicating that the proliferative signal is delivered through cell surface interactions of MTECl cells and thymocytes. Phenotype analysis on FACS of viable thymocytes after coculture revealed that MTECl cells preferentially activate the subsets of CD4+ CDS', CD4+ CD8+ and CD4- CD8- thymocytes; whereas MTEC1- SN preferentially maintained the viability of CD4+ CD8- and CD4-CD8+ thymocyte subsets.For the Con A-activated thymocytes, both MTEC1 cells and MTEC1-SN provided accessory signal(s) to significantly increase the number of viable cells and to markedly enhance the proliferation of thymocytes with virtually equal potency, phenotyped as CD4+CD8-, CD4-CD8+, and CD4- CD8- subsets. In summary, MTEC1 cells displayedselective support to the different thymocyte subsets , and the selectivity is dependent on the status of thymocytes.
文摘Thymic epithelial tumors(TETs) are uncommon neoplasms with a wide range of anatomical, clinical, histological and molecular malignant entities. To date the management of TETs within clinical practice is based on a multimodal therapeutic strategy including surgery, chemotherapy and radiotherapy with a multidisciplinary approach and prognostic evaluation is mainly based on Masaoka staging and World Health Organization classification. Therefore novel strategies are needed, especially for refractory and/or recurrent TETs and for thymic carcinomas that present a poor prognosis. Personalized approaches are currely being developed and molecular targets are emerging from recent integrated genomic analyses. Targeted therapy will represent an important treatment option for TETs with an aggressive histology. To date, data indicate that vascular endothelial growth factor molecules, insulinlike growth factor 1 receptor, cyclin-dependent kinases and mammalian target of rapamycin may be potentially useful as targeted biological therapies.
文摘It has been reported that atopic dermatitis (AD) and ulcerative colitis are related. However, the mechanism underlying this association has not been clarified. We therefore explored how AD induces ulcerative colitis. We developed an AD mouse model (NC/Nga mice) with ulcerative colitis by administering dextran sodium sulfate (DSS) for five days. DSS-induced ulcerative colitis was deteriorated in our conventional AD mouse model compared with specific-pathogen-free (SPF) mice. The plasma levels of thymic stromal lymphopoietin (TSLP) and tumor necrosis factor-α increased the most in DSS-treated conventional mice. Furthermore, the expression of dendritic cells (DC), retinoid-related orphan receptor (ROR)γt (marker of T helper 17 cells [Th17]), interleukin (IL)-17, GATA binding protein 3 (GATA3) (marker of Th2), and IL-4 increased the most in the colon of the DSS-treated conventional mice compared with DSS-treated SPF mice. In addition, TSLP inhibitor (TSLP neutralizing antibody) did not exacerbate ulcerative colitis in DSS-treated conventional mice. These results indicate that TSLP/DC/Th2 and Th17 play major roles in the exacerbation of ulcerative colitis by AD.
