Blown Away: The Unexpected Role of Lymphotoxin in Lymphoid Organ Development

Cyster, Jason G.

doi:10.4049/jimmunol.1400059

Cited by 9 publications

(10 citation statements)

References 32 publications

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“…43,44 The expression of LTa, LTb, and LTbR mRNAs was assessed in response to pro-inflammatory cytokines (Figure 3, Supplementary Figure S3 and S4 online). In HK-2 cells, TNF stimulation significantly induced LTb mRNA after 6, 12, and 24 h (Figure 3b LTbR mRNA expression was abundant in both HK-2 cells (mean Ct 25.6, range 24-34) as well as in HMCs (Ct: 25.3, range [24][25][26][27][28][29]. No changes in LTbR expression were observed throughout the examined period (not illustrated).…”

Section: Expression Of Lts and Ltbr In Human Renal Cells In Vitromentioning

confidence: 87%

The lymphotoxin β receptor is a potential therapeutic target in renal inflammation

Seleznik

Seeger

Bauer

et al. 2016

Kidney International

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Accumulation of inflammatory cells in different renal compartments is a hallmark of progressive kidney diseases including glomerulonephritis (GN). Lymphotoxin β receptor (LTβR) signaling is crucial for the formation of lymphoid tissue, and inhibition of LTβR signaling has ameliorated several non-renal inflammatory models. Therefore, we tested whether LTβR signaling could also have a role in renal injury. Renal biopsies from patients with GN were found to express both LTα and LTβ ligands, as well as LTβR. The LTβR protein and mRNA were localized to tubular epithelial cells, parietal epithelial cells, crescents, and cells of the glomerular tuft, whereas LTβ was found on lymphocytes and tubular epithelial cells. Human tubular epithelial cells, mesangial cells, and mouse parietal epithelial cells expressed both LTα and LTβ mRNA upon stimulation with TNF in vitro. Several chemokine mRNAs and proteins were expressed in response to LTβR signaling. Importantly, in a murine lupus model, LTβR blockade improved renal function without the reduction of serum autoantibody titers or glomerular immune complex deposition. Thus, a preclinical mouse model and human studies strongly suggest that LTβR signaling is involved in renal injury and may be a suitable therapeutic target in renal diseases.

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Section: Expression Of Lts and Ltbr In Human Renal Cells In Vitromentioning

confidence: 87%

The lymphotoxin β receptor is a potential therapeutic target in renal inflammation

Seleznik

Seeger

Bauer

et al. 2016

Kidney International

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“…Thus, the biology of LTβR signaling can only be fully appreciated if its expression inside and outside the tissue of interest is considered. In addition, the two faces of LTβR signaling should also be taken into account when the LTβR pathway is therapeutically targeted [16, 11]. For example, when mice are temporarily treated with a LTβR antagonist, lymph node cell numbers decrease by 10 x 10 6 (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…They facilitate activation and clonal expansion of T cells, as well as their subsequent interaction with B cells [3, 4] which is necessary for pathogen recognition [5], elimination, and memory formation [6]. The lymphotoxin β-receptor (LTβR) pathway is not only involved in the export of T cells from the thymus [7], but is one of the main regulators of secondary lymphoid organ formation [8, 9, 10, 11]. It is expressed in lymphoid but also non-lymphoid organs [12] by non-hematopoietic stromal cells [13], endothelial cells [14], dendritic cells [15], and monocytes [16, 17].…”

Section: Introductionmentioning

confidence: 99%

Growth of Murine Splenic Tissue Is Suppressed by Lymphotoxin β-Receptor Signaling (LTβR) Originating from Splenic and Non-Splenic Tissues

Milićević¹,

Nohroudi

Friederike

et al. 2016

PLoS ONE

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Development and maintenance of secondary lymphoid organs such as lymph nodes and spleen essentially depend on lymphotoxin β-receptor (LTβR) signaling. It is unclear, however, by which molecular mechanism their size is limited. Here, we investigate whether the LTβR pathway is also growth suppressing. By using splenic tissue transplantation it is possible to analyze a potential contribution of LTβR signaling inside and outside of the implanted tissue. We show that LTβR signaling within the endogenous spleen and within non-splenic tissues both significantly suppressed the regeneration of implanted splenic tissue. The suppressive activity positively correlated with the total number of LTβR expressing cells in the animal (regenerate weights of 115 ± 8 mg in LTβR deficient recipients and of 12 ± 9 mg in wild-type recipients), affected also developed splenic tissue, and was induced but not executed via LTβR signaling. Two-dimensional differential gel electrophoresis and subsequent mass spectrometry of stromal splenic tissue was applied to screen for potential factors mediating the LTβR dependent suppressive activity. Thus, LTβR dependent growth suppression is involved in regulating the size of secondary lymphoid organs, and might be therapeutically used to eradicate tertiary lymphoid tissues during autoimmune diseases.

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“…LT-alpha exists as a soluble homotrimer (LTa3) and as a membrane-bound heterotrimeric complex with lymphotoxin beta (LT-beta). LT-beta-deficient mice lack peripheral lymph nodes and Peyer's patches and possess a disorganized splenic architecture with complete loss of germinal centers and FDCs [3,4]. Unlike LT-alpha-deficient mice, LT-beta b-deficient mice have mesenteric lymph nodes (MLNs).…”

Section: Introductionmentioning

confidence: 98%

Essential role of TNF-alpha in development of spleen fibroblastic reticular cells

Zhao

Chen

Liu

et al. 2015

Cellular Immunology

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Blown Away: The Unexpected Role of Lymphotoxin in Lymphoid Organ Development

Cited by 9 publications

References 32 publications

The lymphotoxin β receptor is a potential therapeutic target in renal inflammation

The lymphotoxin β receptor is a potential therapeutic target in renal inflammation

Growth of Murine Splenic Tissue Is Suppressed by Lymphotoxin β-Receptor Signaling (LTβR) Originating from Splenic and Non-Splenic Tissues

Essential role of TNF-alpha in development of spleen fibroblastic reticular cells

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