Stat3 Signaling Promotes Survival And Maintenance Of Medullary Thymic Epithelial Cells

PLoS Genetics
Dakshayani LomadaEllen R Richie

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 reg...Continue Reading

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Citations

Mar 10, 2018·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Feng Zhu, Yinling Hu
Oct 21, 2018·Scandinavian Journal of Immunology·Yu GaoLili Zou
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Feb 23, 2020·Frontiers in Immunology·Hong-Xia WangYu-Rong Qiu
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Oct 8, 2020·Cells·Javier García-CecaAgustín G Zapata
Apr 10, 2021·Nature Communications·Andrea FariniYvan Torrente
Apr 6, 2021·Frontiers in Immunology·Yu GaoMartin E Rottenberg
Sep 19, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhanfeng LiangYong Zhao
Dec 7, 2021·Frontiers in Immunology·Kosuke MiyauchiMasato Kubo

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Methods Mentioned

BETA
transgenic
FACS
enzymatic dissociation
electrophoresis
PCR

Software Mentioned

Image Scope
Aperio
FlowJo
Aperio Scanscope

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