AIM: To investigate the correlation between expression of calreticulin and infiltration of lymphocytes in stage ⅢB colon cancer. METHODS: Sixty-eight pathologically-confirmed speci-mens were obtained from stage ⅢB (...AIM: To investigate the correlation between expression of calreticulin and infiltration of lymphocytes in stage ⅢB colon cancer. METHODS: Sixty-eight pathologically-confirmed speci-mens were obtained from stage ⅢB (T3N1M0) colon cancer patients who underwent radical resection between January 1999 and May 2002 at the Cancer Center of Sun Yat-Sen University, Guangzhou, China. Immuno-histochemical analysis was performed to show infiltration of lymphocytes and expression of calreticulin in colon cancer. Association between calreticulin expression, infiltration of lymphocytes, and 5-year survival rate of patients was assessed. RESULTS: The expression level of calreticulin was lower in cancer nest than in its adjacent normal epithelium since 61.8% (42/68) of the samples were stained with calreticulin in colon cancer. The expression of calreticulin in colon cancer was associated with the infi ltration of CD45RO+ cells rather than with that of CD3+ cells. In addition, the stronger expression of calreticulin and the higher infiltration of CD3+ and CD45RO+ cells in colon cancer were associated with the higher 5-year survival rate of patients. CONCLUSION: Expression of calreticulin is associated with infiltration of T-cells, which implies that a low expression level of molecular marker may represent a new mechanism underlying immune escape in colon cancer.展开更多
AIM: To generate recombinant adenoviral vector con-taining calreticulin (CRT)-hepatitis B surface antigen (HBsAg) fusion gene for developing a safe, effective and HBsAg-specific therapeutic vaccine.METHODS: CRT and HB...AIM: To generate recombinant adenoviral vector con-taining calreticulin (CRT)-hepatitis B surface antigen (HBsAg) fusion gene for developing a safe, effective and HBsAg-specific therapeutic vaccine.METHODS: CRT and HBsAg gene were fused using polymerase chain reaction (PCR), endonuclease diges-tion and ligation methods. The fusion gene was cloned into pENTR/D-TOPO transfer vector after the base pairs of DNA (CACC) sequence was added to the 5′ end. Adenoviral expression vector containing CRT-HBsAg fusion gene was constructed by homologous recombinan-tion. The human embryo kidney (HEK) 293A cells were transfected with linearized DNA plasmid of the recombi-nant adenoviral vector to package and amplify recombi-nant adenovirus. The recombinant adenovirus titer was characterized using the end-dilution assay. The expres-sion of the CRT/HBsAg fusion protein in Ad-CRT/HBsAg infected 293A cells was detected by Western blotting.RESULTS: The CRT-HBsAg fusion gene was char-acterized by PCR and sequencing and its length and sequence were confirmed to be accurate. The CRT-HB-sAg fusion gene recombinant pENTR/D-TOPO transfer vector was constructed. The recombinant adenoviral vector, Ad-CRT/HBsAg, was generated successfully. The titer of Ad-CRT/HBsAg was characterized as 3.9 × 1011 pfu/mL. The CRT-HBsAg fusion protein was ex-pressed by HEK 293A cells correctly. CONCLUSION: CRT/HBsAg fusion gene recombinant replication-defective adenovirus expression vector is constructed successfully and this study has provided an experimental basis for further studies of Hepatitis B vi-rus gene therapy.展开更多
Objective： To investigate the recombinant calreticulin （rCRT） mediated antitumor immune response. Methods： Cell proliferation was determined by MTT method, apoptosis was evaluated by DNA fragmentation and CRT expr...Objective： To investigate the recombinant calreticulin （rCRT） mediated antitumor immune response. Methods： Cell proliferation was determined by MTT method, apoptosis was evaluated by DNA fragmentation and CRT expression and cell localization were assayed by western blotting, QT-RT-PCR and immunofluorescence assays. The mouse melanoma cell line B16-F1 was treated with polyamine analogue BENS to induce apoptosis and incubated with rCRT to get rCRT coated on the membrane, and then the cells were used to immune BALB/c mice as a cell-antigen. Immunized animals were rechallenged by live B16-F1 cells and then tumor generation ratio and the lactate dehydrogenase release assay were used to evaluate antitumor effects of rCRT-mediated immunity. Results： BENS induced apoptosis of B16-F1 cells without the redistribution of CRT within the cells. When B16-F1 cells coated with rCRT were used as cell-antigen to inoculate the animals, the mice obtained the ability in inhibiting proliferation of homologous tumor cells in vivo. Comparing with the positive control group, the splenocytes from those inoculated mice have an obvious enhancement on their cytolytic effects specifically against B16-F1 cells. Conclusion： rCRT coated on the cell surface can enhance immunogenicity of apoptotic tumor cells and mediated effective anti-tumor immunoresponse in mice.展开更多
Calreticulin(CRT)is a highly conserved Ca2+-binding protein and chaperone in the endoplasmic reticulum,which mainly participates in adjusting calcium level and directing proper conformation of proteins.Here,we cloned ...Calreticulin(CRT)is a highly conserved Ca2+-binding protein and chaperone in the endoplasmic reticulum,which mainly participates in adjusting calcium level and directing proper conformation of proteins.Here,we cloned the crt gene of the scleractinian coral Galaxea astreata,named Gacrt,and analysed its ability to drive bacterial agglutination.The full-length Gacrt cDNA consisted of 1792 nucleotides and contained a 77 bp 5’untranslated region(UTR),a 380 bp 3’UTR and a 1335 bp open reading frame(ORF)that encoded a 444 amino acid protein.The deduced peptide possessed a signal peptide domain,an endoplasmic reticulum retrieval signal sequence(KDEL),two potential calreticulin family signature motifs and a set of triplicate repeats.We also found that the recombinant GaCRT protein could promote agglutination of both the Gram-positive bacterium Micrococcus luteus and the Gram-negative bacterium Escherichia coli.These results show that the GaCRT protein can enhance bacterial agglutination,hinting that GaCRT is an immune-relevant molecule involved in host defense against bacterium.展开更多
Background： Calreticulin （CRT） is major Ca^2＋-binding chaperone mainly resident in the endoplasmic reticulum （ER） lumen. Recently, it has been shown that non-ER CRT regulates a wide array of cellular responses. ...Background： Calreticulin （CRT） is major Ca^2＋-binding chaperone mainly resident in the endoplasmic reticulum （ER） lumen. Recently, it has been shown that non-ER CRT regulates a wide array of cellular responses. We previously found that CRT was up-regulated during hypoxia/ reoxygenation （H/R） and this study was aimed to investigate whether CRT nuclear translocation aggravates ER stress （ERS）-associated apoptosis during H/R injury in neonatal rat cardiomyocytes. Methods： Apoptosis rate and lactate dehydrogenase （LDH） leakage in culture medium were measured as indices of cell injury. lmmunofluorescence staining showed the morphological changes of ER and intracellular translocation of CRT. Western blotting or reverse transcription polymerase chain reaction was used to detect the expression of target molecules. Results： Compared with control, H/R increased apoptosis rate and LDH activity. The ER became condensed and bubbled, and CRT translocated to the nucleus. Western blotting showed up-regulation of CRT, Nrf2, activating transcription factor 4 （ATF4）, CHOP and caspase-12 expression after H/R. Exogenous CRT overexpression induced by plasmid transfection before H/R increased cell apoptosis, LDH leakage, ER disorder, CRT nuclear translocation and the expression of ERS-associated molecules. However, administration of the ERS inhibitor, taurine, or CRT siRNA alleviated cell injury, ER disorder, and inhibited ERS-associated apoptosis. Conclusions： Our results indicated that during H/R stress, CRT translocation increases cell apoptosis and LDH leakage, aggravates ER disorder, up-regulates expression of nuclear transcription factors, Nrf2 and ATF4, and activates ERS-associated apoptosis.展开更多
Calreticulin is a unique calcium-binding protein with multiple functions mostly located in the sarcoplasmic/endoplasmic reticulum. A large amount of calcium is absorbed from the medium and transported to mineralizatio...Calreticulin is a unique calcium-binding protein with multiple functions mostly located in the sarcoplasmic/endoplasmic reticulum. A large amount of calcium is absorbed from the medium and transported to mineralization sites during biomineralization in pearl oyster. This paper describes the cloning of the full-length cDNA of calreticulin from Pinctada fucata, namely PCRT. PCRT encodes a deduced 414-amino acid protein, which includes a predicted 17- amino acid signal peptide and an endoplasmic reticulum retrieval sequence HDEL. The protein shows 63%-76% sequence identity and shares some common characteristics with calreticulins from other species. Semi-quantitative RT-PCR indicates that PCRT is ubiquitously expressed in all tissues tested with the highest expression in the hemolymph and the mantle. In situ hybridization analysis of PCRT in the mantle showed strong signals in the inner fold, the inner side of middle fold, and the inner side of outer fold of the mantle epithelium, All these results suggest PCRT might be involved in Ca^2＋ transport and storage during oyster biomineralization.展开更多
研究重组人钙网蛋白(recombinant human calreticulin,rh-CRT)促雄激素性脱发(androgenetic alopecia,AGA)小鼠毛发再生的作用。建立AGA小鼠模型,局部应用rh-CRT,研究rh-CRT对毛发再生的影响。通过观察不同时间毛发整体外观和局部外观...研究重组人钙网蛋白(recombinant human calreticulin,rh-CRT)促雄激素性脱发(androgenetic alopecia,AGA)小鼠毛发再生的作用。建立AGA小鼠模型,局部应用rh-CRT,研究rh-CRT对毛发再生的影响。通过观察不同时间毛发整体外观和局部外观评估毛发的再生,采用颜色测试仪检测皮肤的黑色素指数,利用皮肤镜观察不同类型毛发直径的变化,扫描电镜检测毛小皮的改变,并进一步通过HE染色研究皮肤和真皮脂肪厚度以及毛囊的数量。结果发现,rh-CRT促进AGA小鼠毛发的再生,增加黑色素指数,并显著提高AGA小鼠粗毛和细毛的直径,修复睾酮组(testosterone,TES)诱导的毛小皮的损伤。从皮肤冠状面观察发现rh-CRT显著促进AGA小鼠毛囊数量的表达,并增加皮肤和真皮脂肪的厚度。这些结果表明rh-CRT可以促进AGA小鼠毛发的再生,在防脱产品中具有重要的应用价值。展开更多
Background： Recently, calreticulin （CALR） gene mutations have been identified in patients with essential thrombocythemia （ET）. A high-frequency of ET cases without Janus kinase 2 （JAK2） mutations contain CALR m...Background： Recently, calreticulin （CALR） gene mutations have been identified in patients with essential thrombocythemia （ET）. A high-frequency of ET cases without Janus kinase 2 （JAK2） mutations contain CALR mutations and exhibit clinical characteristics different from those with mutant JAK2. Thus, we investigated the frequency and clinical features of Chinese patients of Han ethnicity with CALR mutations in ET. Methods： We recruited 310 Chinese patients of Han ethnicity with ET to analyze states of CALR, JAK2 V617F, and MPLW5 15 mutations by polymerase chain reaction and direct sequencing. We analyzed the relationship between the mutations and clinical features. Results： CALR, JAK2V617E and MPLW515 mutations were detected in 30% （n = 92）, 48% （n = 149）, and 1% （n = 4） of patients with ET, respectively. The mutation types of CALR involved deletion and insertion of base pairs. Most of them were Type 1 （52-bp deletion） and Type 2 （5-bp insertion, TTGTC） mutations, leading to de1367fs46 and ins385fs47, respectively. The three mutations were exclusive. Clinically, patients with mutated CALR had a lower hemoglobin level, lower white blood cell （WBC） count, and higher platelet count compared to those with mutated JAK2 （P 〈 0.05）. Furthermore, a significant difference was found in WBCs between wild-type patients （triple negative for JAK2, MPL, and CALR mutations） and patients with JAK2 mutations. Patients with CA LR mutations predominantly clustered into low or intermediate groups according to the International Prognostic Score of thrombosis for ET （P 〈 0.05）. Conclusions： CALR mutations were frequent in Chinese patients with ET, especially in those without JAK2 or MPL mutations. Compared withJAK2 mutant ET, CALR mutant ET showed a different clinical manifestation and an unfavorable prognosis. Thus, C4LR is a potentially valuable diagnostic marker and therapeutic target in ET.展开更多
Calreticulin(CRT)is a multifunctional molecule in both intracellular and extracellular environment.We have previ-ously found that a recombinant CRT fragment(rCRT/39-272)could modulate T cell-mediated immunity in mice ...Calreticulin(CRT)is a multifunctional molecule in both intracellular and extracellular environment.We have previ-ously found that a recombinant CRT fragment(rCRT/39-272)could modulate T cell-mediated immunity in mice via activation and expansion of CD1dhiCD5+B cells as well as induction of CRT-specifi c regulatory antibodies.Anti-body secreting cells(ASCs)are terminally differentiated B cells responsible for producing antibodies to participate in positive immune response as well as immune regula-tion.In this study,we demonstrate that rCRT/39-272 dif-ferentiates murine CD1dhiCD5+B cells into ASCs mark-ed by increased expression of plasma cell-associated transcription factors and production of polyreactive antibodies against DNA and CRT in vitro.Intraperitoneal administration of rCRT/39-272 augmented differentiation of CD1dhiCD5+B cells into ASCs in naïve mice or mice with experimental autoimmune encephalomyelitis.Thus,we propose that ASC differentiation and subsequent an-tibody production of CD1dhiCD5+B cells are key steps in CRT-mediated immunoregulation on infl ammatory T cell responses.展开更多
基金Supported by National Nature Science Foundation of China, 30972882Key Projects of Science and Technology of Guang-dong Province, China, 2008B030301079
文摘AIM: To investigate the correlation between expression of calreticulin and infiltration of lymphocytes in stage ⅢB colon cancer. METHODS: Sixty-eight pathologically-confirmed speci-mens were obtained from stage ⅢB (T3N1M0) colon cancer patients who underwent radical resection between January 1999 and May 2002 at the Cancer Center of Sun Yat-Sen University, Guangzhou, China. Immuno-histochemical analysis was performed to show infiltration of lymphocytes and expression of calreticulin in colon cancer. Association between calreticulin expression, infiltration of lymphocytes, and 5-year survival rate of patients was assessed. RESULTS: The expression level of calreticulin was lower in cancer nest than in its adjacent normal epithelium since 61.8% (42/68) of the samples were stained with calreticulin in colon cancer. The expression of calreticulin in colon cancer was associated with the infi ltration of CD45RO+ cells rather than with that of CD3+ cells. In addition, the stronger expression of calreticulin and the higher infiltration of CD3+ and CD45RO+ cells in colon cancer were associated with the higher 5-year survival rate of patients. CONCLUSION: Expression of calreticulin is associated with infiltration of T-cells, which implies that a low expression level of molecular marker may represent a new mechanism underlying immune escape in colon cancer.
基金Supported by Grants from National Natural Science Foundation of China, No. 30901344
文摘AIM: To generate recombinant adenoviral vector con-taining calreticulin (CRT)-hepatitis B surface antigen (HBsAg) fusion gene for developing a safe, effective and HBsAg-specific therapeutic vaccine.METHODS: CRT and HBsAg gene were fused using polymerase chain reaction (PCR), endonuclease diges-tion and ligation methods. The fusion gene was cloned into pENTR/D-TOPO transfer vector after the base pairs of DNA (CACC) sequence was added to the 5′ end. Adenoviral expression vector containing CRT-HBsAg fusion gene was constructed by homologous recombinan-tion. The human embryo kidney (HEK) 293A cells were transfected with linearized DNA plasmid of the recombi-nant adenoviral vector to package and amplify recombi-nant adenovirus. The recombinant adenovirus titer was characterized using the end-dilution assay. The expres-sion of the CRT/HBsAg fusion protein in Ad-CRT/HBsAg infected 293A cells was detected by Western blotting.RESULTS: The CRT-HBsAg fusion gene was char-acterized by PCR and sequencing and its length and sequence were confirmed to be accurate. The CRT-HB-sAg fusion gene recombinant pENTR/D-TOPO transfer vector was constructed. The recombinant adenoviral vector, Ad-CRT/HBsAg, was generated successfully. The titer of Ad-CRT/HBsAg was characterized as 3.9 × 1011 pfu/mL. The CRT-HBsAg fusion protein was ex-pressed by HEK 293A cells correctly. CONCLUSION: CRT/HBsAg fusion gene recombinant replication-defective adenovirus expression vector is constructed successfully and this study has provided an experimental basis for further studies of Hepatitis B vi-rus gene therapy.
基金supported by a grant from the National Natural Science Foundation of China (No.30973445)
文摘Objective： To investigate the recombinant calreticulin （rCRT） mediated antitumor immune response. Methods： Cell proliferation was determined by MTT method, apoptosis was evaluated by DNA fragmentation and CRT expression and cell localization were assayed by western blotting, QT-RT-PCR and immunofluorescence assays. The mouse melanoma cell line B16-F1 was treated with polyamine analogue BENS to induce apoptosis and incubated with rCRT to get rCRT coated on the membrane, and then the cells were used to immune BALB/c mice as a cell-antigen. Immunized animals were rechallenged by live B16-F1 cells and then tumor generation ratio and the lactate dehydrogenase release assay were used to evaluate antitumor effects of rCRT-mediated immunity. Results： BENS induced apoptosis of B16-F1 cells without the redistribution of CRT within the cells. When B16-F1 cells coated with rCRT were used as cell-antigen to inoculate the animals, the mice obtained the ability in inhibiting proliferation of homologous tumor cells in vivo. Comparing with the positive control group, the splenocytes from those inoculated mice have an obvious enhancement on their cytolytic effects specifically against B16-F1 cells. Conclusion： rCRT coated on the cell surface can enhance immunogenicity of apoptotic tumor cells and mediated effective anti-tumor immunoresponse in mice.
基金The National Marine Welfare Industry Research Project under contract No.201105012the Guangdong Provincial Natural Science Foundation under contract No.S2011010000269+1 种基金the Guangdong Marine Fishery Science and Technology Extension Project under contract No.A201308E02the Guangdong Ocean University Scientific Research Start-up Fund for the Doctoral Program under contract No.R17066。
文摘Calreticulin(CRT)is a highly conserved Ca2+-binding protein and chaperone in the endoplasmic reticulum,which mainly participates in adjusting calcium level and directing proper conformation of proteins.Here,we cloned the crt gene of the scleractinian coral Galaxea astreata,named Gacrt,and analysed its ability to drive bacterial agglutination.The full-length Gacrt cDNA consisted of 1792 nucleotides and contained a 77 bp 5’untranslated region(UTR),a 380 bp 3’UTR and a 1335 bp open reading frame(ORF)that encoded a 444 amino acid protein.The deduced peptide possessed a signal peptide domain,an endoplasmic reticulum retrieval signal sequence(KDEL),two potential calreticulin family signature motifs and a set of triplicate repeats.We also found that the recombinant GaCRT protein could promote agglutination of both the Gram-positive bacterium Micrococcus luteus and the Gram-negative bacterium Escherichia coli.These results show that the GaCRT protein can enhance bacterial agglutination,hinting that GaCRT is an immune-relevant molecule involved in host defense against bacterium.
基金This study was supported by the National Natural Science Foundation of China （No. 81170140 and No. 31471094）.
文摘Background： Calreticulin （CRT） is major Ca^2＋-binding chaperone mainly resident in the endoplasmic reticulum （ER） lumen. Recently, it has been shown that non-ER CRT regulates a wide array of cellular responses. We previously found that CRT was up-regulated during hypoxia/ reoxygenation （H/R） and this study was aimed to investigate whether CRT nuclear translocation aggravates ER stress （ERS）-associated apoptosis during H/R injury in neonatal rat cardiomyocytes. Methods： Apoptosis rate and lactate dehydrogenase （LDH） leakage in culture medium were measured as indices of cell injury. lmmunofluorescence staining showed the morphological changes of ER and intracellular translocation of CRT. Western blotting or reverse transcription polymerase chain reaction was used to detect the expression of target molecules. Results： Compared with control, H/R increased apoptosis rate and LDH activity. The ER became condensed and bubbled, and CRT translocated to the nucleus. Western blotting showed up-regulation of CRT, Nrf2, activating transcription factor 4 （ATF4）, CHOP and caspase-12 expression after H/R. Exogenous CRT overexpression induced by plasmid transfection before H/R increased cell apoptosis, LDH leakage, ER disorder, CRT nuclear translocation and the expression of ERS-associated molecules. However, administration of the ERS inhibitor, taurine, or CRT siRNA alleviated cell injury, ER disorder, and inhibited ERS-associated apoptosis. Conclusions： Our results indicated that during H/R stress, CRT translocation increases cell apoptosis and LDH leakage, aggravates ER disorder, up-regulates expression of nuclear transcription factors, Nrf2 and ATF4, and activates ERS-associated apoptosis.
基金the National Natural Science Foundation of China (Nos. 30371092, 30221003, and 30530600)
文摘Calreticulin is a unique calcium-binding protein with multiple functions mostly located in the sarcoplasmic/endoplasmic reticulum. A large amount of calcium is absorbed from the medium and transported to mineralization sites during biomineralization in pearl oyster. This paper describes the cloning of the full-length cDNA of calreticulin from Pinctada fucata, namely PCRT. PCRT encodes a deduced 414-amino acid protein, which includes a predicted 17- amino acid signal peptide and an endoplasmic reticulum retrieval sequence HDEL. The protein shows 63%-76% sequence identity and shares some common characteristics with calreticulins from other species. Semi-quantitative RT-PCR indicates that PCRT is ubiquitously expressed in all tissues tested with the highest expression in the hemolymph and the mantle. In situ hybridization analysis of PCRT in the mantle showed strong signals in the inner fold, the inner side of middle fold, and the inner side of outer fold of the mantle epithelium, All these results suggest PCRT might be involved in Ca^2＋ transport and storage during oyster biomineralization.
文摘研究重组人钙网蛋白(recombinant human calreticulin,rh-CRT)促雄激素性脱发(androgenetic alopecia,AGA)小鼠毛发再生的作用。建立AGA小鼠模型,局部应用rh-CRT,研究rh-CRT对毛发再生的影响。通过观察不同时间毛发整体外观和局部外观评估毛发的再生,采用颜色测试仪检测皮肤的黑色素指数,利用皮肤镜观察不同类型毛发直径的变化,扫描电镜检测毛小皮的改变,并进一步通过HE染色研究皮肤和真皮脂肪厚度以及毛囊的数量。结果发现,rh-CRT促进AGA小鼠毛发的再生,增加黑色素指数,并显著提高AGA小鼠粗毛和细毛的直径,修复睾酮组(testosterone,TES)诱导的毛小皮的损伤。从皮肤冠状面观察发现rh-CRT显著促进AGA小鼠毛囊数量的表达,并增加皮肤和真皮脂肪的厚度。这些结果表明rh-CRT可以促进AGA小鼠毛发的再生,在防脱产品中具有重要的应用价值。
文摘Background： Recently, calreticulin （CALR） gene mutations have been identified in patients with essential thrombocythemia （ET）. A high-frequency of ET cases without Janus kinase 2 （JAK2） mutations contain CALR mutations and exhibit clinical characteristics different from those with mutant JAK2. Thus, we investigated the frequency and clinical features of Chinese patients of Han ethnicity with CALR mutations in ET. Methods： We recruited 310 Chinese patients of Han ethnicity with ET to analyze states of CALR, JAK2 V617F, and MPLW5 15 mutations by polymerase chain reaction and direct sequencing. We analyzed the relationship between the mutations and clinical features. Results： CALR, JAK2V617E and MPLW515 mutations were detected in 30% （n = 92）, 48% （n = 149）, and 1% （n = 4） of patients with ET, respectively. The mutation types of CALR involved deletion and insertion of base pairs. Most of them were Type 1 （52-bp deletion） and Type 2 （5-bp insertion, TTGTC） mutations, leading to de1367fs46 and ins385fs47, respectively. The three mutations were exclusive. Clinically, patients with mutated CALR had a lower hemoglobin level, lower white blood cell （WBC） count, and higher platelet count compared to those with mutated JAK2 （P 〈 0.05）. Furthermore, a significant difference was found in WBCs between wild-type patients （triple negative for JAK2, MPL, and CALR mutations） and patients with JAK2 mutations. Patients with CA LR mutations predominantly clustered into low or intermediate groups according to the International Prognostic Score of thrombosis for ET （P 〈 0.05）. Conclusions： CALR mutations were frequent in Chinese patients with ET, especially in those without JAK2 or MPL mutations. Compared withJAK2 mutant ET, CALR mutant ET showed a different clinical manifestation and an unfavorable prognosis. Thus, C4LR is a potentially valuable diagnostic marker and therapeutic target in ET.
基金This study was supported by grants from PCSIRT(IRT1075)the National Natural Science Foundation of China(Grant Nos.31370908,31070781,and 31100633)+1 种基金the National Basic Research Program(973 Program)(No.2010CB529102)Foundation of Nature Science of Jiangsu Higher Education Institutions of China(11KJB180011).
文摘Calreticulin(CRT)is a multifunctional molecule in both intracellular and extracellular environment.We have previ-ously found that a recombinant CRT fragment(rCRT/39-272)could modulate T cell-mediated immunity in mice via activation and expansion of CD1dhiCD5+B cells as well as induction of CRT-specifi c regulatory antibodies.Anti-body secreting cells(ASCs)are terminally differentiated B cells responsible for producing antibodies to participate in positive immune response as well as immune regula-tion.In this study,we demonstrate that rCRT/39-272 dif-ferentiates murine CD1dhiCD5+B cells into ASCs mark-ed by increased expression of plasma cell-associated transcription factors and production of polyreactive antibodies against DNA and CRT in vitro.Intraperitoneal administration of rCRT/39-272 augmented differentiation of CD1dhiCD5+B cells into ASCs in naïve mice or mice with experimental autoimmune encephalomyelitis.Thus,we propose that ASC differentiation and subsequent an-tibody production of CD1dhiCD5+B cells are key steps in CRT-mediated immunoregulation on infl ammatory T cell responses.
