Differential requirement for CCR4 and CCR7 during the development of innate and adaptive αβT cells in the adult thymus

Research output: Contribution to journalArticlepeer-review

Standard

Differential requirement for CCR4 and CCR7 during the development of innate and adaptive αβT cells in the adult thymus. / Cowan, Jennifer E; McCarthy, Nicholas I; Parnell, Sonia M; White, Andrea J; Bacon, Andrea; Serge, Arnauld; Irla, Magali; Lane, Peter J L; Jenkinson, Eric J; Jenkinson, William; Anderson, Graham.

In: Journal of Immunology, Vol. 193, No. 3, 01.08.2014, p. 1204-12.

Research output: Contribution to journalArticlepeer-review

Harvard

APA

Vancouver

Author

Bibtex

@article{34f1998b125b497e942f1cc6a2f23590,
title = "Differential requirement for CCR4 and CCR7 during the development of innate and adaptive αβT cells in the adult thymus",
abstract = "αβT cell development depends upon serial migration of thymocyte precursors through cortical and medullary microenvironments, enabling specialized stromal cells to provide important signals at specific stages of their development. Although conventional αβT cells are subject to clonal deletion in the medulla, entry into the thymus medulla also fosters αβT cell differentiation. For example, during postnatal periods, the medulla is involved in the intrathymic generation of multiple αβT cell lineages, notably the induction of Foxp3(+) regulatory T cell development and the completion of invariant NKT cell development. Although migration of conventional αβT cells to the medulla is mediated by the chemokine receptor CCR7, how other T cell subsets gain access to medullary areas during their normal development is not clear. In this study, we show that combining a panel of thymocyte maturation markers with cell surface analysis of CCR7 and CCR4 identifies distinct stages in the development of multiple αβT cell lineages in the thymus. Although Aire regulates expression of the CCR4 ligands CCL17 and CCL22, we show that CCR4 is dispensable for thymocyte migration and development in the adult thymus, demonstrating defective T cell development in Aire(-/-) mice is not because of a loss of CCR4-mediated migration. Moreover, we reveal that CCR7 controls the development of invariant NKT cells by enabling their access to IL-15 trans-presentation in the thymic medulla and influences the balance of early and late intrathymic stages of Foxp3(+) regulatory T cell development. Collectively, our data identify novel roles for CCR7 during intrathymic T cell development, highlighting its importance in enabling multiple αβT cell lineages to access the thymic medulla.",
keywords = "Adaptive Immunity, Animals, Biological Markers, Cell Differentiation, Cell Lineage, Epithelial Cells, Immunity, Innate, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptors, Antigen, T-Cell, alpha-beta, Receptors, CCR4, Receptors, CCR7, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory, Thymus Gland",
author = "Cowan, {Jennifer E} and McCarthy, {Nicholas I} and Parnell, {Sonia M} and White, {Andrea J} and Andrea Bacon and Arnauld Serge and Magali Irla and Lane, {Peter J L} and Jenkinson, {Eric J} and William Jenkinson and Graham Anderson",
note = "Copyright {\textcopyright} 2014 The Authors.",
year = "2014",
month = aug,
day = "1",
doi = "10.4049/jimmunol.1400993",
language = "English",
volume = "193",
pages = "1204--12",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

RIS

TY - JOUR

T1 - Differential requirement for CCR4 and CCR7 during the development of innate and adaptive αβT cells in the adult thymus

AU - Cowan, Jennifer E

AU - McCarthy, Nicholas I

AU - Parnell, Sonia M

AU - White, Andrea J

AU - Bacon, Andrea

AU - Serge, Arnauld

AU - Irla, Magali

AU - Lane, Peter J L

AU - Jenkinson, Eric J

AU - Jenkinson, William

AU - Anderson, Graham

N1 - Copyright © 2014 The Authors.

PY - 2014/8/1

Y1 - 2014/8/1

N2 - αβT cell development depends upon serial migration of thymocyte precursors through cortical and medullary microenvironments, enabling specialized stromal cells to provide important signals at specific stages of their development. Although conventional αβT cells are subject to clonal deletion in the medulla, entry into the thymus medulla also fosters αβT cell differentiation. For example, during postnatal periods, the medulla is involved in the intrathymic generation of multiple αβT cell lineages, notably the induction of Foxp3(+) regulatory T cell development and the completion of invariant NKT cell development. Although migration of conventional αβT cells to the medulla is mediated by the chemokine receptor CCR7, how other T cell subsets gain access to medullary areas during their normal development is not clear. In this study, we show that combining a panel of thymocyte maturation markers with cell surface analysis of CCR7 and CCR4 identifies distinct stages in the development of multiple αβT cell lineages in the thymus. Although Aire regulates expression of the CCR4 ligands CCL17 and CCL22, we show that CCR4 is dispensable for thymocyte migration and development in the adult thymus, demonstrating defective T cell development in Aire(-/-) mice is not because of a loss of CCR4-mediated migration. Moreover, we reveal that CCR7 controls the development of invariant NKT cells by enabling their access to IL-15 trans-presentation in the thymic medulla and influences the balance of early and late intrathymic stages of Foxp3(+) regulatory T cell development. Collectively, our data identify novel roles for CCR7 during intrathymic T cell development, highlighting its importance in enabling multiple αβT cell lineages to access the thymic medulla.

AB - αβT cell development depends upon serial migration of thymocyte precursors through cortical and medullary microenvironments, enabling specialized stromal cells to provide important signals at specific stages of their development. Although conventional αβT cells are subject to clonal deletion in the medulla, entry into the thymus medulla also fosters αβT cell differentiation. For example, during postnatal periods, the medulla is involved in the intrathymic generation of multiple αβT cell lineages, notably the induction of Foxp3(+) regulatory T cell development and the completion of invariant NKT cell development. Although migration of conventional αβT cells to the medulla is mediated by the chemokine receptor CCR7, how other T cell subsets gain access to medullary areas during their normal development is not clear. In this study, we show that combining a panel of thymocyte maturation markers with cell surface analysis of CCR7 and CCR4 identifies distinct stages in the development of multiple αβT cell lineages in the thymus. Although Aire regulates expression of the CCR4 ligands CCL17 and CCL22, we show that CCR4 is dispensable for thymocyte migration and development in the adult thymus, demonstrating defective T cell development in Aire(-/-) mice is not because of a loss of CCR4-mediated migration. Moreover, we reveal that CCR7 controls the development of invariant NKT cells by enabling their access to IL-15 trans-presentation in the thymic medulla and influences the balance of early and late intrathymic stages of Foxp3(+) regulatory T cell development. Collectively, our data identify novel roles for CCR7 during intrathymic T cell development, highlighting its importance in enabling multiple αβT cell lineages to access the thymic medulla.

KW - Adaptive Immunity

KW - Animals

KW - Biological Markers

KW - Cell Differentiation

KW - Cell Lineage

KW - Epithelial Cells

KW - Immunity, Innate

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Receptors, Antigen, T-Cell, alpha-beta

KW - Receptors, CCR4

KW - Receptors, CCR7

KW - T-Lymphocyte Subsets

KW - T-Lymphocytes, Regulatory

KW - Thymus Gland

U2 - 10.4049/jimmunol.1400993

DO - 10.4049/jimmunol.1400993

M3 - Article

C2 - 24990081

VL - 193

SP - 1204

EP - 1212

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -