IL-7-producing stromal cells are critical for lymph node remodeling

Lucas Onder; Priyanka Narang; Elke Scandella; Qian Chai; Maria Iolyeva; Kerim Hoorweg; Cornelia Halin; Ellen Richie; Paul Kaye; Jürgen Westermann; Tom Cupedo; Mark Coles; Burkhard Ludewig

doi:10.1182/blood-2012-03-416859

IL-7-producing stromal cells are critical for lymph node remodeling

Lucas Onder, Priyanka Narang, Elke Scandella, Qian Chai, Maria Iolyeva, Kerim Hoorweg, Cornelia Halin, Ellen Richie, Paul Kaye, Jürgen Westermann, Tom Cupedo, Mark Coles, Burkhard Ludewig

Research output: Contribution to journal › Article › peer-review

Abstract

Non-hematopoietic stromal cells of secondary lymphoid organs form important scaffold and fluid transport structures such as lymph node trabeculae, lymph vessels, and conduits. Furthermore, through the production of chemokines and cytokines, these cells generate a particular microenvironment that determines lymphocyte positioning and supports lymphocyte homeostasis. Interleukin-7 (IL-7) is an important stromal cell-derived cytokine that has been considered to be derived mainly from T cell zone fibroblastic reticular cells (FRCs). We show here that lymphatic endothelial cells (LECs) are a prominent source of IL-7 both in human and murine lymph nodes. Using BAC transgenic IL-7-Cre mice, we found that FRCs and LECs strongly upregulated IL-7 expression during LN remodeling following viral infection and LN reconstruction after avascular transplantation. Furthermore, IL-7-producing stromal cells contributed to de novo formation of LyveI-positive lymphatic structures connecting reconstructed LNs with the surrounding tissue. Importantly, diphtheria toxin-mediated depletion of IL-7-producing stromal cells completely abolished LN reconstruction. Taken together, this study identifies LN LECs as a major source of IL-7 and shows that IL-7-producing stromal cells are critical for reconstruction and remodeling of the distinct LN microenvironment.

Original language	English
Pages (from-to)	4675-4683
Number of pages	9
Journal	Blood
Volume	120
Issue number	24
DOIs	https://doi.org/10.1182/blood-2012-03-416859
Publication status	Published - 6 Dec 2012

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10.1182/blood-2012-03-416859

http://bloodjournal.hematologylibrary.org/content/120/24/4675

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title = "IL-7-producing stromal cells are critical for lymph node remodeling",

abstract = "Non-hematopoietic stromal cells of secondary lymphoid organs form important scaffold and fluid transport structures such as lymph node trabeculae, lymph vessels, and conduits. Furthermore, through the production of chemokines and cytokines, these cells generate a particular microenvironment that determines lymphocyte positioning and supports lymphocyte homeostasis. Interleukin-7 (IL-7) is an important stromal cell-derived cytokine that has been considered to be derived mainly from T cell zone fibroblastic reticular cells (FRCs). We show here that lymphatic endothelial cells (LECs) are a prominent source of IL-7 both in human and murine lymph nodes. Using BAC transgenic IL-7-Cre mice, we found that FRCs and LECs strongly upregulated IL-7 expression during LN remodeling following viral infection and LN reconstruction after avascular transplantation. Furthermore, IL-7-producing stromal cells contributed to de novo formation of LyveI-positive lymphatic structures connecting reconstructed LNs with the surrounding tissue. Importantly, diphtheria toxin-mediated depletion of IL-7-producing stromal cells completely abolished LN reconstruction. Taken together, this study identifies LN LECs as a major source of IL-7 and shows that IL-7-producing stromal cells are critical for reconstruction and remodeling of the distinct LN microenvironment.",

author = "Lucas Onder and Priyanka Narang and Elke Scandella and Qian Chai and Maria Iolyeva and Kerim Hoorweg and Cornelia Halin and Ellen Richie and Paul Kaye and J{\"u}rgen Westermann and Tom Cupedo and Mark Coles and Burkhard Ludewig",

year = "2012",

month = dec,

day = "6",

doi = "10.1182/blood-2012-03-416859",

language = "English",

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T1 - IL-7-producing stromal cells are critical for lymph node remodeling

AU - Onder, Lucas

AU - Narang, Priyanka

AU - Scandella, Elke

AU - Chai, Qian

AU - Iolyeva, Maria

AU - Hoorweg, Kerim

AU - Halin, Cornelia

AU - Richie, Ellen

AU - Kaye, Paul

AU - Westermann, Jürgen

AU - Cupedo, Tom

AU - Coles, Mark

AU - Ludewig, Burkhard

PY - 2012/12/6

Y1 - 2012/12/6

N2 - Non-hematopoietic stromal cells of secondary lymphoid organs form important scaffold and fluid transport structures such as lymph node trabeculae, lymph vessels, and conduits. Furthermore, through the production of chemokines and cytokines, these cells generate a particular microenvironment that determines lymphocyte positioning and supports lymphocyte homeostasis. Interleukin-7 (IL-7) is an important stromal cell-derived cytokine that has been considered to be derived mainly from T cell zone fibroblastic reticular cells (FRCs). We show here that lymphatic endothelial cells (LECs) are a prominent source of IL-7 both in human and murine lymph nodes. Using BAC transgenic IL-7-Cre mice, we found that FRCs and LECs strongly upregulated IL-7 expression during LN remodeling following viral infection and LN reconstruction after avascular transplantation. Furthermore, IL-7-producing stromal cells contributed to de novo formation of LyveI-positive lymphatic structures connecting reconstructed LNs with the surrounding tissue. Importantly, diphtheria toxin-mediated depletion of IL-7-producing stromal cells completely abolished LN reconstruction. Taken together, this study identifies LN LECs as a major source of IL-7 and shows that IL-7-producing stromal cells are critical for reconstruction and remodeling of the distinct LN microenvironment.

AB - Non-hematopoietic stromal cells of secondary lymphoid organs form important scaffold and fluid transport structures such as lymph node trabeculae, lymph vessels, and conduits. Furthermore, through the production of chemokines and cytokines, these cells generate a particular microenvironment that determines lymphocyte positioning and supports lymphocyte homeostasis. Interleukin-7 (IL-7) is an important stromal cell-derived cytokine that has been considered to be derived mainly from T cell zone fibroblastic reticular cells (FRCs). We show here that lymphatic endothelial cells (LECs) are a prominent source of IL-7 both in human and murine lymph nodes. Using BAC transgenic IL-7-Cre mice, we found that FRCs and LECs strongly upregulated IL-7 expression during LN remodeling following viral infection and LN reconstruction after avascular transplantation. Furthermore, IL-7-producing stromal cells contributed to de novo formation of LyveI-positive lymphatic structures connecting reconstructed LNs with the surrounding tissue. Importantly, diphtheria toxin-mediated depletion of IL-7-producing stromal cells completely abolished LN reconstruction. Taken together, this study identifies LN LECs as a major source of IL-7 and shows that IL-7-producing stromal cells are critical for reconstruction and remodeling of the distinct LN microenvironment.

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U2 - 10.1182/blood-2012-03-416859

DO - 10.1182/blood-2012-03-416859

M3 - Article

C2 - 22955921

SN - 0006-4971

VL - 120

SP - 4675

EP - 4683

JO - Blood

JF - Blood

IS - 24

ER -

IL-7-producing stromal cells are critical for lymph node remodeling

Abstract

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