title: An Essential Role for the Transcription Factor Runx1 in T Cell Maturation.
abstract: The transcription factor Runx1 has essential roles throughout hematopoiesis. Here, we demonstrate that Runx1 is critical for T cell maturation. Peripheral naïve CD4(+) T cells from CD4-cre Runx1 cKO mice are phenotypically and functionally immature as shown by decreased production of TNF-α upon TCR stimulation. The loss of peripheral CD4(+) T cells in CD4-cre Runx1 cKO mice is not due to defects in homeostasis or decreased expression of IL-7Rα, as transgenic expression of IL-7Rα does not rescue the loss of CD4(+) T cells. Rather, immature Runx1-deficient CD4(+) T cells are eliminated in the periphery by the activation and fixation of the classical complement pathway. In the thymus, there is a severe block in all aspects of intrathymic T cell maturation, although both positive and negative selection are unaltered. Thus, loss of Runx1 leads to the earliest characterized block in post-positive selection intrathymic maturation of CD4 T cells.
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN, United States.
authors.forename: Fan-Chi
authors.initials: FC
authors.lastname: Hsu
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN, United States.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Shapiro
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN, United States.
authors.forename: Barsha
authors.initials: B
authors.lastname: Dash
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN, United States.
authors.forename: Chien-Chang
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN, United States.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Constans
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN, United States.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Chung
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN, United States.
authors.forename: Sinibaldo R
authors.initials: SR
authors.lastname: Romero Arocha
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN, United States.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Belmonte
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN, United States.
authors.forename: Meibo W
authors.initials: MW
authors.lastname: Chen
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN, United States.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: McWilliams
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN, United States.
authors.forename: Virginia Smith
authors.initials: VS
authors.lastname: Shapiro
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D003171:Complement Pathway, Classical / Q000502:physiology; D003165:Complement System Proteins / Q000378:metabolism; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005434:Flow Cytometry; D006031:Glycosylation; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000378:metabolism / Q000502:physiology*; D060168:Thymocytes / Q000166:cytology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D020395:Receptors, Interleukin-7; C493726:Runx1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C415350:interleukin-7 receptor, alpha chain; D003165:Complement System Proteins; D019158:N-Acetylneuraminic Acid