Visualization of Lymphotoxin-β and Lymphotoxin-β Receptor Expression in Mouse Embryos

Browning, Jeffrey L.; French, Lars E.

doi:10.4049/jimmunol.168.10.5079

Cited by 81 publications

(55 citation statements)

References 45 publications

(69 reference statements)

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“…In addition, the tissue infiltrates and autoantibodies in LT-deficient mice have provoked speculation that the pathway may be involved in central tolerance induction. Thymocytes express the ligands LT␣1␤2 (13) and LIGHT (14), while LT␤R is displayed by medullary epithelial cells (MECs) (15). MECs are thymic stromal cells that also express a wide array of peripheral tissue Ags (PTAs) (16), many of whose RNA transcripts are controlled by the transcriptional regulator Aire (17).…”

Section: Ymphtoxin (Lt)mentioning

confidence: 99%

Lymphotoxin Pathway and Aire Influences on Thymic Medullary Epithelial Cells Are Unconnected

Venanzi

Gray²,

Benoist³

et al. 2007

The Journal of Immunology

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The lymphotoxin pathway is critical for the development and maintenance of peripheral lymphoid organs. Mice with deficiencies in members of this pathway lack lymph nodes and Peyer’s patches and have abnormal spleen architecture. These animals also develop autoantibodies to and lymphocytic infiltrates of multiple organs, provoking speculation that the lymphotoxin pathway may play a role in central tolerance induction. Indeed, a series of reports has claimed that lymphotoxin signals control the expression of Aire, a transcriptional regulator that is expressed in medullary epithelial cells of the thymus, mediates ectopic transcription of genes encoding a variety of peripheral tissue Ags, and promotes clonal deletion of self-reactive thymocytes. However, one report argued that lymphotoxin signals regulate the composition and organization of the thymus, particularly of the medullary epithelial compartment. Herein, we resolve this controversy in favor of the latter view. The expression and function of Aire were unaffected in medullary epithelial cells of mice lacking either lymphotoxin β receptor or the lymphotoxin α-chain, and there was minimal overlap between the sets of genes controlled by Aire and lymphotoxin. Instead, both knockout lines showed abnormal medullary epithelial cell organization, and the line lacking the β receptor had significantly fewer medullary epithelial cells. In short, the lymphotoxin pathway drives the developmental rather than selectional properties of thymic stromal cells.

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Section: Ymphtoxin (Lt)mentioning

confidence: 99%

Lymphotoxin Pathway and Aire Influences on Thymic Medullary Epithelial Cells Are Unconnected

Venanzi

Gray²,

Benoist³

et al. 2007

The Journal of Immunology

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“…However, earlier studies already suggest the LTβR expression by cells of the myeloid lineage [46][47][48]. LTβR expression on activated pulmonary macrophages and thioglycolate-elicited peritoneal macrophages is crucial for host defense [49].…”

Section: Functions In Host Defense Regulated By Tnfr Superfamilymentioning

confidence: 99%

The TNF receptor and Ig superfamily members form an integrated signaling circuit controlling dendritic cell homeostasis

Trez

Ware

2008

Cytokine & Growth Factor Reviews

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Dendritic cells (DC) constitute the most potent antigen presenting cells of the immune system, playing a key role bridging innate and adaptive immune responses. Specialized DC subsets differ depending on their origin, tissue location and the influence of trophic factors, the latter remain to be fully understood. Stromal cell and myeloid-associated Lymphotoxin-β receptor (LTβR) signaling is required for the local proliferation of lymphoid tissue DC. This review focuses the LTβR signaling cascade as a crucial positive trophic signal in the homeostasis of DC subsets. The noncanonical coreceptor pathway comprised of the Immunoglobulin (Ig) superfamily member, B and T lymphocyte attenuator (BTLA) and TNFR superfamily member, Herpesvirus entry mediator (HVEM) counter regulates the trophic signaling by LTβR. Together both pathways form an integrated signaling circuit achieving homeostasis of DC subsets.Keywords dendritic cells; homeostasis; TNF superfamily; cosignaling; lymphotoxin; herpesvirus entry mediator Dendritic CellsDendritic cells (DC) originate from hematopoietic precursors and can be divided in several subsets depending on their anatomical location, surface phenotype and function. For example, two broad classes of DC are the peripheral migratory DC and the lymphoid tissue-resident DC [1]. The migratory DC, i.e. the dermal DC and Langerhans cells, can be considered as sentinels of the immune system as they form a sensing barrier in peripheral tissues at the interface with environment. The lymphoid tissue-resident DC include the splenic and thymic DC.Dendritic cells are specialized in the capture, transport, processing and presentation of antigens. In the presence of a microbial stimulus, these steps are associated with further DC differentiation (maturation) characterized by upregulation of costimulatory and major histocompatibility complex (MHC) molecules. As DC become activated they migrate to or Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Both spleen and lymph node lymphoid tissue-resident DC possess a half-life of about three days. Despite their rapid turnover, little is known about the factors controlling immediate precursors and homeostasis in vivo. In earlier studies, CD8α expression was used to distinguish between "lymphoid" and "myeloid" DC. However, more recent experiments showed that different DC subsets could differentiate from both lymphoid and myeloid precursors [6,7]. CD8α marker remains very useful to discriminate between subsets, but no longer defines a subset origin. Recently, the group of Shortman provided in vivo and in vitro evidence fo...

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“…In the adult immune system, the LT pathway appears to involve communication between subsets of ligand-positive lymphocytes and receptor-positive monocytic, dendritic, and stromal cells (8). In general, this pathway maintains certain microenvironments in the secondary lymphoid organs via the regulation of several specialized reticular stromal cell networks (9,10).…”

Section: T He Lymphotoxin (Lt)mentioning

confidence: 99%

A Role for the Lymphotoxin/LIGHT Axis in the Pathogenesis of Murine Collagen-Induced Arthritis

Fava

Notidis

Hunt

et al. 2003

The Journal of Immunology

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112

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A lymphotoxin-β (LTβ) receptor-Ig fusion protein (LTβR-Ig) was used to evaluate the importance of the lymphotoxin/LIGHT axis in the development and perpetuation of arthritis. Prophylactic treatment with the inhibitor protein LTβR-Ig blocked the induction of collagen-induced arthritis in mice and adjuvant arthritis in Lewis rats. Treatment of mice with established collagen-induced arthritis reduced the severity of arthritic symptoms and joint tissue damage. However, in a passive model of anti-collagen Ab-triggered arthritis, joint inflammation was not affected by LTβR-Ig treatment precluding LT/LIGHT involvement in the very terminal immune complex/complement/FcR-mediated effector phase. Collagen-II and Mycobacterium-specific T cell responses were not impaired, yet there was evidence that the overall response to the mycobacterium was blunted. Serum titers of anti-collagen-II Abs were reduced especially during the late phase of disease. Treatment with LTβR-Ig ablated follicular dendritic cell networks in the draining lymph nodes, suggesting that impaired class switching and affinity maturation may have led to a decreased level of pathological autoantibodies. These data are consistent with a model in which the LT/LIGHT axis controls microenvironments in the draining lymph nodes. These environments are critical in shaping the adjuvant-driven initiating events that impact the subsequent quality of the anti-collagen response in the later phases. Consequently, blockade of the LT/LIGHT axis may represent a novel approach to the treatment of autoimmune diseases such as rheumatoid arthritis that involve both T cell and Ab components.

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Visualization of Lymphotoxin-β and Lymphotoxin-β Receptor Expression in Mouse Embryos

Cited by 81 publications

References 45 publications

Lymphotoxin Pathway and Aire Influences on Thymic Medullary Epithelial Cells Are Unconnected

Lymphotoxin Pathway and Aire Influences on Thymic Medullary Epithelial Cells Are Unconnected

The TNF receptor and Ig superfamily members form an integrated signaling circuit controlling dendritic cell homeostasis

A Role for the Lymphotoxin/LIGHT Axis in the Pathogenesis of Murine Collagen-Induced Arthritis

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