Redefining thymus medulla specialization for central tolerance

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Redefining thymus medulla specialization for central tolerance. / Cosway, Emilie J; Lucas, Beth; James, Kieran D; Parnell, Sonia M; Carvalho-Gaspar, Manuela; White, Andrea J; Tumanov, Alexei V; Jenkinson, William; Anderson, Graham.

In: The Journal of Experimental Medicine, Vol. 214, No. 11, 22.08.2017, p. 3183-3195.

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@article{f2bd262e101d4548b603def5eb49684e,
title = "Redefining thymus medulla specialization for central tolerance",
abstract = "During αβT cell development, the thymus medulla represents an essential microenvironment for T cell tolerance. This functional specialization is attributed to its typical organized topology consisting of a branching structure that contains medullary thymic epithelial cell (mTEC) networks to support negative selection and Foxp3(+) T-regulatory cell (T-reg) development. Here, by performing TEC-specific deletion of the thymus medulla regulator lymphotoxin β receptor (LTβR), we show that thymic tolerance mechanisms operate independently of LTβR-mediated mTEC development and organization. Consistent with this, mTECs continue to express Fezf2 and Aire, regulators of intrathymic self-antigens, and support T-reg development despite loss of LTβR-mediated medulla organogenesis. Moreover, we demonstrate that LTβR controls thymic tolerance by regulating the frequency and makeup of intrathymic dendritic cells (DCs) required for effective thymocyte negative selection. In all, our study demonstrates that thymus medulla specialization for thymic tolerance segregates from medulla organogenesis and instead involves LTβR-mediated regulation of the thymic DC pool.",
author = "Cosway, {Emilie J} and Beth Lucas and James, {Kieran D} and Parnell, {Sonia M} and Manuela Carvalho-Gaspar and White, {Andrea J} and Tumanov, {Alexei V} and William Jenkinson and Graham Anderson",
note = "{\textcopyright} 2017 Cosway et al.",
year = "2017",
month = aug,
day = "22",
doi = "10.1084/jem.20171000",
language = "English",
volume = "214",
pages = "3183--3195",
journal = "The Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "11",

}

RIS

TY - JOUR

T1 - Redefining thymus medulla specialization for central tolerance

AU - Cosway, Emilie J

AU - Lucas, Beth

AU - James, Kieran D

AU - Parnell, Sonia M

AU - Carvalho-Gaspar, Manuela

AU - White, Andrea J

AU - Tumanov, Alexei V

AU - Jenkinson, William

AU - Anderson, Graham

N1 - © 2017 Cosway et al.

PY - 2017/8/22

Y1 - 2017/8/22

N2 - During αβT cell development, the thymus medulla represents an essential microenvironment for T cell tolerance. This functional specialization is attributed to its typical organized topology consisting of a branching structure that contains medullary thymic epithelial cell (mTEC) networks to support negative selection and Foxp3(+) T-regulatory cell (T-reg) development. Here, by performing TEC-specific deletion of the thymus medulla regulator lymphotoxin β receptor (LTβR), we show that thymic tolerance mechanisms operate independently of LTβR-mediated mTEC development and organization. Consistent with this, mTECs continue to express Fezf2 and Aire, regulators of intrathymic self-antigens, and support T-reg development despite loss of LTβR-mediated medulla organogenesis. Moreover, we demonstrate that LTβR controls thymic tolerance by regulating the frequency and makeup of intrathymic dendritic cells (DCs) required for effective thymocyte negative selection. In all, our study demonstrates that thymus medulla specialization for thymic tolerance segregates from medulla organogenesis and instead involves LTβR-mediated regulation of the thymic DC pool.

AB - During αβT cell development, the thymus medulla represents an essential microenvironment for T cell tolerance. This functional specialization is attributed to its typical organized topology consisting of a branching structure that contains medullary thymic epithelial cell (mTEC) networks to support negative selection and Foxp3(+) T-regulatory cell (T-reg) development. Here, by performing TEC-specific deletion of the thymus medulla regulator lymphotoxin β receptor (LTβR), we show that thymic tolerance mechanisms operate independently of LTβR-mediated mTEC development and organization. Consistent with this, mTECs continue to express Fezf2 and Aire, regulators of intrathymic self-antigens, and support T-reg development despite loss of LTβR-mediated medulla organogenesis. Moreover, we demonstrate that LTβR controls thymic tolerance by regulating the frequency and makeup of intrathymic dendritic cells (DCs) required for effective thymocyte negative selection. In all, our study demonstrates that thymus medulla specialization for thymic tolerance segregates from medulla organogenesis and instead involves LTβR-mediated regulation of the thymic DC pool.

U2 - 10.1084/jem.20171000

DO - 10.1084/jem.20171000

M3 - Article

C2 - 28830910

VL - 214

SP - 3183

EP - 3195

JO - The Journal of Experimental Medicine

JF - The Journal of Experimental Medicine

SN - 0022-1007

IS - 11

ER -