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RNA editing enzyme ADAR1 is required for early t cell development

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Blood Science 2020年第1期2卷 27-32页

作者： Richard Xufeng Daibang Nie Qiong Yang Wang Wang tao Cheng Qingde Wang Department of Surgery University of Pittsburgh200 Lothrop StreetPittsburghPA 15213USA Humancells Biosciences SunnyvaleCA 94089USA Department of Immunology College of Basic MedicineChongqing Medical UniversityChongqing 400016China State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesInstitute of Hematology and Blood Diseases HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300020China

the RNA editing enzyme ADAR1 has been shown to be an essential molecule for hematopoietic cell differentiation,embryonic development,and regulation of immune ***,we present evidence in a t-cell-specific gene knockout mouse model that ADAR1 is required for early t cell *** of ADAR1 led to cell death of the progenitors at the double negative stage and prevented t cell maturation in the ***,ADAR1 deletion in pre-t cells preferentially affected tCRb-expressing cells causing tCRb positive cell *** of IFN signaling occurred in the premature t cells,indicating a role of IFN signaling in the survival of tCRb-expressing cells regulated by *** study demonstrated an essential role for the RNA editing enzyme ADAR1 as a potential regulator for t-cell fate determination during clonal selection,which,in turn,contributes to immunologic homeostasis.

关键词： ADAR1 Conditional knockout RNA editing t cell development

thymic-specific regulation of tCR signaling by tespa1

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cellular & Molecular Immunology 2019年第12期16卷 897-907页

作者： Jun Lyu Pengfei Wang ting Xu Yichao Shen Zejin Cui Mingzhu Zheng Guo Fu Linrong Lu Institute of Immunology and Department of Dermatology and Rheumatology at Sir Run Run Shaw Hospital Zhejiang University School of Medicine310058 HangzhouChina Program in Molecular and cellular Biology Zhejiang University School of Medicine310058 HangzhouChina State Key Laboratory of cellular Stress Biology School of Life SciencesXiamen University361005 FujianChina ZJU-UoE Institute Zhejiang University School of Medicine310058 HangzhouChina Innovation Center for cell Signaling Networks Zhejiang University School of Medicine310058 HangzhouChina Dr.Li Dak Sum&Yip Yio Chin Center for Stem cell and Regenerative Medicine Zhejiang University School of Medicine310058 HangzhouChina

Double-positive(DP)thymocytes undergo positive selection to become mature single-positive CD4+and CD8+t cells in response to t cell receptor(tCR)*** mature t cells,DP cells must respond to low-affinity self-peptide-MHC ligands before full upregulation of their surface tCR expression can ***,DP thymocytes must be more sensitive to ligands than mature t cells.A number of molecules have been found that are able to enhance the strength of the tCR signal to facilitate positive ***,almost all of these molecules are also active in mature t ***(thymocyte expressed molecule involved in selection)and tespa1(thymocyte expressed positive selection associated 1)are two recently discovered molecules essential for optimal tCR signaling and thymocyte development.A deficiency in both molecules leads to defects in positive ***,we compared the relative contributions of themis and tespa1 to positive selection in *** show that tespa1 deficiency led to more limited and specific gene expression profile changes in cells undergoing positive *** mixed bone marrow transfer experiments,tespa1^(−/−)cells showed more severe defects in thymocyte development than themis^(−/−)***,tespa1^(−/−)cells showed a substantial degree of homeostatic expansion and became predominant in the peripheral lymphoid organs,suggesting that tespa1 is a thymic-specific tCR signaling *** hypothesis is further supported by our observations in tespa1 conditional knockout mice,as tespa1 deletion in peripheral t cells did not affect tCR signaling or cell *** different regulatory effects of tespa1 and themis are in accordance with their nonredundant roles in thymocyte selection,during which tespa1 and themis double knockouts showed additive defects.

关键词： t cell development Positive selection tCR signaling

trap1a is an X-linked and cell-intrinsic regulator of thymocyte development

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cellular & Molecular Immunology 2017年第8期14卷 685-692页

作者： Chi-Shan Li Fei tang Peng Zhang taijiao Jiang thomas L Saunders Pan Zheng Yang Liu Institute of Biomedical Sciences Academia SinicaTaipeiTaiwanChina Center for Cancer and Immunology Research Children’s National Medical CenterWashingtonDCUSA Institute of Biophysics Chinese Academy of ScienceBeijingChina Department of Internal Medicine School of MedicineUniversity of MichiganAnn ArborMIUSA

the X-linked trap1a gene encodes the tumor rejection antigen P1A,which is expressed in fetal tissues and multiple lineages of tumor *** function of this gene remains *** chimeric mice with wild-type(Wt)and trap1a^(−/y)bone marrow,we show that trap1a^(−/y)donor cells are capable of generating most lineages of hematopoietic cells,with the notable exception of t *** of trap1a selectively arrests t-cell development at double-negative stage 1(DN1,with a CD4^(−)CD8^(−)CD25^(−)CD44^(+)phenotype).Because trap1a is expressed in Lin^(−)Sca-1^(+)c-Kit^(+)and common lymphoid progenitors but not in immature thymocytes(DN1-DN4),trap1a mutations affect the differentiation potential of progenitor cells without directly acting on t *** a similarity in the blockade of DN1 to DN2 transition,the trap1a^(−/y)DN1 cells have normal expression of c-Kit,in contrast to what was reported in the Notch1^(−/−)*** DNA profiling of trap1a^(−/y)and Wt embryonic stem cells shows that trap1a does not regulate the Notch *** data reveal that trap1a is an X-linked regulator that affects the differentiation potential of progenitor cells into t cells through a Notch-independent mechanism and identify an important function for the trap1a gene.

关键词： Notch tumor antigens t cell development

Study on the role of tRIM69 in lymphocytes development and macrophage function

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Study on the role of TRIM69 in lymphocytes development and m...

Sel1L deficiency promotes th1 and th17 differentiation and exacerbates the development of EAE

第九届全国免疫学学术大会

作者： Ji Xu He Kangxia Zhang Siya Zhang Jianmin He Wei Department of Immunology State Key Laboratory of Medical Molecular BiologySchool of Basic MedicinePeking Union Medical College Institute of Basic Medical Sciences

Background:tRIM69,an E3 ubiquitin ligase which contains classical RBCC domians,is a canonical tripartite motif containing protein and could induce apoptosis in cells when *** tRIM69 has a role in lymphocytes development and macrophage function remains ***:Examine the role of tRIM69 in lymphocytes development and macrophage function in ***:Single cell suspension was isolated from lymphoid nodes(LNs),spleens and thymuses from tRIM69 knocked out(KO)as well as wild type(Wt)mice by passing through 40μm cell *** cytometry was employed to test the subgroup *** macrophage was isolated from Wt and KO mice and was seeded in 24 well plates(3×10/well)and 6 well plates(1×10/well)and stimulated with 100ng/ml LPS,and the cell lysate and culture supernatant were collected and tested by WB and ***:(1)We found the tRIM69mice has the normal breed capacity,and the sizes and proportion of B cells,t cells,CD4,CD8t cells in spleens,thymuses and LNs were normal compared with the Wt mice;(2)the proportion of CD25CD44t cells in the thymus of tRIM69mice were much higher than Wt mice;(3)the phospho-NF-KB in macrophage stimulated with LPS were much more in tRIM69mice than that in Wt ***:tRIM69mice displayed normal proportions of t cells,B cells,αβt cells andγδt cells in spleens,LNs and IELs,but had much more CD25CD44t cells in thymuses,suggesting a regulatory role in t cell development As many other tripartite motif containing proteins,tRIM69 may have a negative role in innate immunity.

关键词： tRIM69 t cell development Intestinal intraepithelial lymphocytes

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Sel1L deficiency promotes Th1 and Th17 differentiation and e...