title: Stat3 Signaling Promotes Survival And Maintenance Of Medullary Thymic Epithelial Cells.
abstract: Medullary thymic epithelial cells (mTECs) are essential for establishing central tolerance by expressing a diverse array of self-peptides that delete autoreactive thymocytes and/or divert thymocytes into the regulatory T cell lineage. Activation of the NFκB signaling pathway in mTEC precursors is indispensable for mTEC maturation and proliferation resulting in proper medullary region formation. Here we show that the Stat3-mediated signaling pathway also plays a key role in mTEC development and homeostasis. Expression of a constitutively active Stat3 transgene targeted to the mTEC compartment increases mTEC cellularity and bypasses the requirement for signals from positively selected thymocytes to drive medullary region formation. Conversely, conditional deletion of Stat3 disrupts medullary region architecture and reduces the number of mTECs. Stat3 signaling does not affect mTEC proliferation, but rather promotes survival of immature MHCIIloCD80lo mTEC precursors. In contrast to striking alterations in the mTEC compartment, neither enforced expression nor deletion of Stat3 affects cTEC cellularity or organization. These results demonstrate that in addition to the NFkB pathway, Stat3-mediated signals play an essential role in regulating mTEC cellularity and medullary region homeostasis.
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park, Smithville, Texas, United States of America.
authors.forename: Dakshayani
authors.initials: D
authors.lastname: Lomada
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park, Smithville, Texas, United States of America.
authors.forename: Manju
authors.initials: M
authors.lastname: Jain
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park, Smithville, Texas, United States of America.|Epigenetics and Molecular Carcinogenesis Graduate Program, The University of Texas Graduate School of Biomedical Sciences Houston, Texas, United States of America.
authors.forename: Michelle
authors.initials: M
authors.lastname: Bolner
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park, Smithville, Texas, United States of America.|Epigenetics and Molecular Carcinogenesis Graduate Program, The University of Texas Graduate School of Biomedical Sciences Houston, Texas, United States of America.
authors.forename: Kaitlin A G
authors.initials: KA
authors.lastname: Reeh
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park, Smithville, Texas, United States of America.
authors.forename: Rhea
authors.initials: R
authors.lastname: Kang
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park, Smithville, Texas, United States of America.
authors.forename: Madhava C
authors.initials: MC
authors.lastname: Reddy
authors.affiliation: Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: DiGiovanni
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park, Smithville, Texas, United States of America.
authors.forename: Ellen R
authors.initials: ER
authors.lastname: Richie
mesh_terms: D000818:Animals; D019013:CD40 Antigens / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D008213:Lymphocyte Activation; D051379:Mice; D016328:NF-kappa B / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D060168:Thymocytes / Q000378:metabolism; D013950:Thymus Gland / Q000254:growth & development / Q000378:metabolism; D019076:Transgenes
chemical_list: D019013:CD40 Antigens; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse