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Lymphotoxin-? receptor signaling through NF-?B2-RelB pathway reprograms adipocyte precursors as lymph node stromal cells.

ABSTRACT: Lymph node development during embryogenesis involves lymphotoxin-? receptor engagement and subsequent differentiation of a poorly defined population of mesenchymal cells into lymphoid tissue organizer cells. Here, we showed that embryonic mesenchymal cells with characteristics of adipocyte precursors present in the microenvironment of lymph nodes gave rise to lymph node organizer cells. Signaling through the lymphotoxin-? receptor controlled the fate of adipocyte precursor cells by blocking adipogenesis and instead promoting lymphoid tissue stromal cell differentiation. This effect involved activation of the NF-?B2-RelB signaling pathway and inhibition of the expression of the key adipogenic factors Ppar? and Cebp?. In vivo organogenesis assays show that embryonic and adult adipocyte precursor cells can migrate into newborn lymph nodes and differentiate into a variety of lymph node stromal cells. Thus, we propose that adipose tissues act as a source of lymphoid stroma for lymph nodes and other lymphoid structures associated with fat.

SUBMITTER: Benezech C

PROVIDER: S-EPMC3809035 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Lymphotoxin-β receptor signaling through NF-κB2-RelB pathway reprograms adipocyte precursors as lymph node stromal cells.

Bénézech Cécile C Mader Emma E Desanti Guillaume G Khan Mahmood M Nakamura Kyoko K White Andrea A Ware Carl F CF Anderson Graham G Caamaño Jorge H JH

Immunity 20120830 4

Lymph node development during embryogenesis involves lymphotoxin-β receptor engagement and subsequent differentiation of a poorly defined population of mesenchymal cells into lymphoid tissue organizer cells. Here, we showed that embryonic mesenchymal cells with characteristics of adipocyte precursors present in the microenvironment of lymph nodes gave rise to lymph node organizer cells. Signaling through the lymphotoxin-β receptor controlled the fate of adipocyte precursor cells by blocking adip ...[more]

PMID: 22940098

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Project description:A growing number of studies has shed light on the role of the NF-?? in non-small-cell lung cancer (NSCLC). To address the significance of major effectors of the NF-?? alternative pathway, we investigated the relationship between NF-??2, RelB, NIK and Bcl3 expression (mRNA and protein) and the clinical outcome of NSCLC patients. NF-??2, RelB, NIK and Bcl3 protein expression levels were assessed by immunohistochemistry in tissue samples from 151 NSCLC patients who had curative resection. mRNA levels were also evaluated in 69 patients using quantitative real-time PCR. Although all studied proteins were overexpressed in NSCLC (P?<?0.001 for all), only RelB mRNA levels were strongly increased in cancerous specimens compared to tumor-adjacent non-neoplastic tissues (P?=?0.009). Moreover, NF-?B2, RelB and Bcl3 expression was associated with overall survival (OS). In particular, cytoplasmic and mRNA expression of RelB was related to 5-year OS (P?=?0.014 and P?=?0.006, respectively). Multivariate analysis also showed that Bcl3 expression (nuclear and cytoplasmic) was associated with increased 5-year OS (P?=?0.002 and P?=?0.036, respectively). In addition, higher Bcl3 mRNA levels were associated with inferior OS in stages I & II and improved OS in stages III and IV after 5-year follow-up (P?=?0.004 and P?=?0.001, respectively). Furthermore, stage I patients with lower NF-?B2 mRNA levels had better 5-year survival in univariate and multivariate analysis (P?=?0.031 and P?=?0.028, respectively). Interestingly, RelB expression (cytoplasmic and mRNA) was inversely associated with relapse rates (P?=?0.027 and P?=?0.015, respectively), while low NIK cytoplasmic expression was associated with lower relapse rates (P?=?0.019). Cytoplasmic NIK expression as well as NF-?B2/ Bcl3 detection was associated with lymph node infiltration (P?=?0.039 and P?=?0.014, respectively). The present study confirms the deregulation of the NF-?B alternative pathway in NSCLC and also demonstrates the importance of this pathway in prognosis, recurrence and infiltration of regional lymph nodes.

Dataset Information

Lymphotoxin-? receptor signaling through NF-?B2-RelB pathway reprograms adipocyte precursors as lymph node stromal cells.

Publications

Lymphotoxin-β receptor signaling through NF-κB2-RelB pathway reprograms adipocyte precursors as lymph node stromal cells.

Similar Datasets

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