Sarah J Miller, Nancy M Gonzalez, Morgan E Smith, Mandy J Croyle, Bradley K Yoder, Kurt A Zimmerman
{"title":"小鼠胸腺细胞的正常分化需要T细胞表达的Ift88。","authors":"Sarah J Miller, Nancy M Gonzalez, Morgan E Smith, Mandy J Croyle, Bradley K Yoder, Kurt A Zimmerman","doi":"10.14814/phy2.70120","DOIUrl":null,"url":null,"abstract":"<p><p>Intraflagellar transport protein 88 (Ift88) is required for the formation of cilia in the thymus and non-ciliary dependent functions including T cell immune synapse formation. To test the role of Ift88 in T cell development, we performed flow cytometry analysis on thymus and spleen tissue isolated from mice lacking Ift88 in thymic epithelial cells (TECs) or T cells. Analyses indicated that TEC Ift88 deletion had no impact on thymic T cell development and minimal impact on splenic T cells. Analysis of T cells in CaggCre<sup>ERT2+</sup>Ift88 <sup>tm1Bky</sup>mTmG mice indicate that approximately half of DN1 thymocytes are Ift88 deficient 3 weeks post-tamoxifen induction; Ift88 loss did not impact T cell development at the DN2-DN4 stage or the CD4+/CD8+ double-positive (DP) thymocyte stage. However, survival of Ift88 deficient T cells was significantly reduced at the single-positive (SP) thymocyte stage, as was the number of CD4+ and CD8+ T cells in spleen and kidney. Despite preferential survival of Ift88-proficient cells, the total number of T cells the in spleen and kidney was minimally impacted by Ift88 loss. These data suggest Ift88 is required for differentiation of DP thymocytes into SP thymocytes and that Ift88 proficient T cells can compensate for deficient cells to fill the open niche.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"12 22","pages":"e70120"},"PeriodicalIF":2.2000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"T cell-expressed Ift88 is required for proper thymocyte differentiation in mice.\",\"authors\":\"Sarah J Miller, Nancy M Gonzalez, Morgan E Smith, Mandy J Croyle, Bradley K Yoder, Kurt A Zimmerman\",\"doi\":\"10.14814/phy2.70120\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Intraflagellar transport protein 88 (Ift88) is required for the formation of cilia in the thymus and non-ciliary dependent functions including T cell immune synapse formation. To test the role of Ift88 in T cell development, we performed flow cytometry analysis on thymus and spleen tissue isolated from mice lacking Ift88 in thymic epithelial cells (TECs) or T cells. Analyses indicated that TEC Ift88 deletion had no impact on thymic T cell development and minimal impact on splenic T cells. Analysis of T cells in CaggCre<sup>ERT2+</sup>Ift88 <sup>tm1Bky</sup>mTmG mice indicate that approximately half of DN1 thymocytes are Ift88 deficient 3 weeks post-tamoxifen induction; Ift88 loss did not impact T cell development at the DN2-DN4 stage or the CD4+/CD8+ double-positive (DP) thymocyte stage. However, survival of Ift88 deficient T cells was significantly reduced at the single-positive (SP) thymocyte stage, as was the number of CD4+ and CD8+ T cells in spleen and kidney. Despite preferential survival of Ift88-proficient cells, the total number of T cells the in spleen and kidney was minimally impacted by Ift88 loss. These data suggest Ift88 is required for differentiation of DP thymocytes into SP thymocytes and that Ift88 proficient T cells can compensate for deficient cells to fill the open niche.</p>\",\"PeriodicalId\":20083,\"journal\":{\"name\":\"Physiological Reports\",\"volume\":\"12 22\",\"pages\":\"e70120\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Physiological Reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.14814/phy2.70120\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHYSIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Physiological Reports","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.14814/phy2.70120","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
胸腺纤毛的形成和非纤毛依赖性功能(包括 T 细胞免疫突触的形成)需要鞘内转运蛋白 88(Ift88)。为了测试 Ift88 在 T 细胞发育中的作用,我们对胸腺上皮细胞(TECs)或 T 细胞中缺乏 Ift88 的小鼠分离出的胸腺和脾脏组织进行了流式细胞术分析。分析表明,TEC Ift88 缺失对胸腺 T 细胞的发育没有影响,对脾脏 T 细胞的影响很小。对 CaggCreERT2+Ift88 tm1BkymTmG 小鼠 T 细胞的分析表明,在他莫昔芬诱导后 3 周,大约一半的 DN1 胸腺细胞缺乏 Ift88;Ift88 缺失不会影响 DN2-DN4 阶段或 CD4+/CD8+ 双阳性 (DP) 胸腺细胞阶段的 T 细胞发育。然而,缺失 Ift88 的 T 细胞在单阳性(SP)胸腺细胞阶段的存活率明显降低,脾脏和肾脏中 CD4+ 和 CD8+ T 细胞的数量也是如此。尽管Ift88缺陷细胞优先存活,但脾脏和肾脏中的T细胞总数受Ift88缺失的影响很小。这些数据表明,DP胸腺细胞分化成SP胸腺细胞需要Ift88,而Ift88熟练的T细胞可以补偿缺乏的细胞,以填补开放的龛位。
T cell-expressed Ift88 is required for proper thymocyte differentiation in mice.
Intraflagellar transport protein 88 (Ift88) is required for the formation of cilia in the thymus and non-ciliary dependent functions including T cell immune synapse formation. To test the role of Ift88 in T cell development, we performed flow cytometry analysis on thymus and spleen tissue isolated from mice lacking Ift88 in thymic epithelial cells (TECs) or T cells. Analyses indicated that TEC Ift88 deletion had no impact on thymic T cell development and minimal impact on splenic T cells. Analysis of T cells in CaggCreERT2+Ift88 tm1BkymTmG mice indicate that approximately half of DN1 thymocytes are Ift88 deficient 3 weeks post-tamoxifen induction; Ift88 loss did not impact T cell development at the DN2-DN4 stage or the CD4+/CD8+ double-positive (DP) thymocyte stage. However, survival of Ift88 deficient T cells was significantly reduced at the single-positive (SP) thymocyte stage, as was the number of CD4+ and CD8+ T cells in spleen and kidney. Despite preferential survival of Ift88-proficient cells, the total number of T cells the in spleen and kidney was minimally impacted by Ift88 loss. These data suggest Ift88 is required for differentiation of DP thymocytes into SP thymocytes and that Ift88 proficient T cells can compensate for deficient cells to fill the open niche.
期刊介绍:
Physiological Reports is an online only, open access journal that will publish peer reviewed research across all areas of basic, translational, and clinical physiology and allied disciplines. Physiological Reports is a collaboration between The Physiological Society and the American Physiological Society, and is therefore in a unique position to serve the international physiology community through quick time to publication while upholding a quality standard of sound research that constitutes a useful contribution to the field.