Expression and splicing of Ikaros family members in murine and human thymocytes |
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| Affiliation: | 1. Laboratório de Imunopatologia, Instituto Butantan, São Paulo, SP, Brazil;2. CIHIDECAR-Departmento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina;3. LIM62–Universidade de São Paulo, São Paulo, Brazil;1. BIT Medical Convergence Graduate Program and Department of Microbiology and Immunology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea;2. Institute of Life Sciences, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea;3. Department of Biological Sciences, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea;1. Department of Dermatology, Southwest Hospital, PLA, Third Military Medical University, Chongqing 400038, China;2. Department of Orthopdics, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037, China;3. Institute of Pathophysiology, PLA, Third Military Medical University, Chongqing 400038, China;1. Jiangsu Key Laboratory for Biodiversity & Biotechnology and Jiangsu Key Laboratory for Aquatic Crustacean Diseases, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Road, Nanjing 210046, PR China;2. Co-Innovation Center for Marine Bio-Industry Technology of Jiangsu Province, Lianyungang, Jiangsu 222005, PR China;3. State Key Laboratory Breeding Base of Marine Genetic Resource, Third Institute of Oceanography, SOA, Xiamen 361005, China |
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| Abstract: | The Ikaros family of transcription factors includes five highly homologous members that can homodimerize or heterodimerize in any combination. Dimerization is essential for their ability to bind DNA and function as transcription factors. Previous studies showed that eliminating the function of the entire family blocks lymphocyte development while deletion of individual family members has relatively minor defects. These data indicate that multiple family members function during T cell development, so we examined the changes in expression of each family member as thymocytes progressed from the CD4−CD8− double negative (DN) to the CD4+CD8+ double positive (DP) developmental stage. Further, we compared the expression of each family member in murine and human thymocytes. In both species, Ikaros and Aiolos mRNA levels increased as thymocytes progressed through the DN to DP transition, but the corresponding increases in protein levels were only observed in mice. Further, Ikaros and Aiolos underwent extensive alternative splicing in mice, whereas only Ikaros was extensively spliced in humans. Helios mRNA and protein levels decreased during murine T cell development, but increased during human T cell development. These differences in the expression and splicing of Ikaros family members between human and murine thymocytes strongly suggest that the Ikaros family of transcription factors regulates murine and human T cell development differently, although the similarities across Ikaros family members may allow different proteins to fulfill similar functions. |
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| Keywords: | T cell development Ikaros Aiolos Helios Human Mice |
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