title: Snai2 and Snai3 transcriptionally regulate cellular fitness and functionality of T cell lineages through distinct gene programs.
abstract: T lymphocytes are essential contributors to the adaptive immune system and consist of multiple lineages that serve various effector and regulatory roles. As such, precise control of gene expression is essential to the proper development and function of these cells. Previously, we identified Snai2 and Snai3 as being essential regulators of immune tolerance partly due to the impaired function of CD4(+) regulatory T cells in Snai2/3 conditional double knockout mice. Here we extend those previous findings using a bone marrow transplantation model to provide an environmentally unbiased view of the molecular changes imparted onto various T lymphocyte populations once Snai2 and Snai3 are deleted. The data presented here demonstrate that Snai2 and Snai3 transcriptionally regulate the cellular fitness and functionality of not only CD4(+) regulatory T cells but effector CD8(α+) and CD4(+) conventional T cells as well. This is achieved through the modulation of gene sets unique to each cell type and includes transcriptional targets relevant to the survival and function of each T cell lineage. As such, Snai2 and Snai3 are essential regulators of T cell immunobiology.
authors.affiliation: Division of Cell Biology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, United States. Electronic address: pdpioli@g.ucla.edu.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Pioli
authors.affiliation: Division of Cell Biology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, United States.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Whiteside
authors.affiliation: Division of Cell Biology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, United States.
authors.forename: Janis J
authors.initials: JJ
authors.lastname: Weis
authors.affiliation: Division of Cell Biology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, United States.
authors.forename: John H
authors.initials: JH
authors.lastname: Weis
mesh_terms: D000818:Animals; D015415:Biomarkers; D019070:Cell Lineage / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation; D007156:Immunologic Memory; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D015415:Biomarkers; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; C000604449:Snai2 protein, mouse; C404767:Snai3 protein, mouse; D000071250:Snail Family Transcription Factors
keywords: Autoimmunity; Genetic deficiency; Snail transcription factors; T cell receptor; T lymphocyte
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