Cargando…

Lymphotoxin α/β and Tumor Necrosis Factor Are Required for Stromal Cell Expression of Homing Chemokines in B and T Cell Areas of the Spleen

Mice deficient in the cytokines tumor necrosis factor (TNF) or lymphotoxin (LT) α/β lack polarized B cell follicles in the spleen. Deficiency in CXC chemokine receptor 5 (CXCR5), a receptor for B lymphocyte chemoattractant (BLC), also causes loss of splenic follicles. Here we report that BLC express...

Descripción completa

Detalles Bibliográficos
Autores principales: Ngo, Vu N., Korner, Heinrich, Gunn, Michael D., Schmidt, Kerstin N., Sean Riminton, D., Cooper, Max D., Browning, Jeffrey L., Sedgwick, Jonathon D., Cyster, Jason G.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192983/
https://www.ncbi.nlm.nih.gov/pubmed/9892622
_version_ 1782147363613179904
author Ngo, Vu N.
Korner, Heinrich
Gunn, Michael D.
Schmidt, Kerstin N.
Sean Riminton, D.
Cooper, Max D.
Browning, Jeffrey L.
Sedgwick, Jonathon D.
Cyster, Jason G.
author_facet Ngo, Vu N.
Korner, Heinrich
Gunn, Michael D.
Schmidt, Kerstin N.
Sean Riminton, D.
Cooper, Max D.
Browning, Jeffrey L.
Sedgwick, Jonathon D.
Cyster, Jason G.
author_sort Ngo, Vu N.
collection PubMed
description Mice deficient in the cytokines tumor necrosis factor (TNF) or lymphotoxin (LT) α/β lack polarized B cell follicles in the spleen. Deficiency in CXC chemokine receptor 5 (CXCR5), a receptor for B lymphocyte chemoattractant (BLC), also causes loss of splenic follicles. Here we report that BLC expression by follicular stromal cells is defective in TNF-, TNF receptor 1 (TNFR1)-, LTα- and LTβ-deficient mice. Treatment of adult mice with antagonists of LTα1β2 also leads to decreased BLC expression. These findings indicate that LTα1β2 and TNF have a role upstream of BLC/CXCR5 in the process of follicle formation. In addition to disrupted follicles, LT-deficient animals have disorganized T zones. Expression of the T cell attractant, secondary lymphoid tissue chemokine (SLC), by T zone stromal cells is found to be markedly depressed in LTα-, and LTβ-deficient mice. Expression of the SLC-related chemokine, Epstein Barr virus–induced molecule 1 ligand chemokine (ELC), is also reduced. Exploring the basis for the reduced SLC expression led to identification of further disruptions in T zone stromal cells. Together these findings indicate that LTα1β2 and TNF are required for the development and function of B and T zone stromal cells that make chemokines necessary for lymphocyte compartmentalization in the spleen.
format Text
id pubmed-2192983
institution National Center for Biotechnology Information
language English
publishDate 1999
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-21929832008-04-16 Lymphotoxin α/β and Tumor Necrosis Factor Are Required for Stromal Cell Expression of Homing Chemokines in B and T Cell Areas of the Spleen Ngo, Vu N. Korner, Heinrich Gunn, Michael D. Schmidt, Kerstin N. Sean Riminton, D. Cooper, Max D. Browning, Jeffrey L. Sedgwick, Jonathon D. Cyster, Jason G. J Exp Med Articles Mice deficient in the cytokines tumor necrosis factor (TNF) or lymphotoxin (LT) α/β lack polarized B cell follicles in the spleen. Deficiency in CXC chemokine receptor 5 (CXCR5), a receptor for B lymphocyte chemoattractant (BLC), also causes loss of splenic follicles. Here we report that BLC expression by follicular stromal cells is defective in TNF-, TNF receptor 1 (TNFR1)-, LTα- and LTβ-deficient mice. Treatment of adult mice with antagonists of LTα1β2 also leads to decreased BLC expression. These findings indicate that LTα1β2 and TNF have a role upstream of BLC/CXCR5 in the process of follicle formation. In addition to disrupted follicles, LT-deficient animals have disorganized T zones. Expression of the T cell attractant, secondary lymphoid tissue chemokine (SLC), by T zone stromal cells is found to be markedly depressed in LTα-, and LTβ-deficient mice. Expression of the SLC-related chemokine, Epstein Barr virus–induced molecule 1 ligand chemokine (ELC), is also reduced. Exploring the basis for the reduced SLC expression led to identification of further disruptions in T zone stromal cells. Together these findings indicate that LTα1β2 and TNF are required for the development and function of B and T zone stromal cells that make chemokines necessary for lymphocyte compartmentalization in the spleen. The Rockefeller University Press 1999-01-18 /pmc/articles/PMC2192983/ /pubmed/9892622 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Ngo, Vu N.
Korner, Heinrich
Gunn, Michael D.
Schmidt, Kerstin N.
Sean Riminton, D.
Cooper, Max D.
Browning, Jeffrey L.
Sedgwick, Jonathon D.
Cyster, Jason G.
Lymphotoxin α/β and Tumor Necrosis Factor Are Required for Stromal Cell Expression of Homing Chemokines in B and T Cell Areas of the Spleen
title Lymphotoxin α/β and Tumor Necrosis Factor Are Required for Stromal Cell Expression of Homing Chemokines in B and T Cell Areas of the Spleen
title_full Lymphotoxin α/β and Tumor Necrosis Factor Are Required for Stromal Cell Expression of Homing Chemokines in B and T Cell Areas of the Spleen
title_fullStr Lymphotoxin α/β and Tumor Necrosis Factor Are Required for Stromal Cell Expression of Homing Chemokines in B and T Cell Areas of the Spleen
title_full_unstemmed Lymphotoxin α/β and Tumor Necrosis Factor Are Required for Stromal Cell Expression of Homing Chemokines in B and T Cell Areas of the Spleen
title_short Lymphotoxin α/β and Tumor Necrosis Factor Are Required for Stromal Cell Expression of Homing Chemokines in B and T Cell Areas of the Spleen
title_sort lymphotoxin α/β and tumor necrosis factor are required for stromal cell expression of homing chemokines in b and t cell areas of the spleen
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192983/
https://www.ncbi.nlm.nih.gov/pubmed/9892622
work_keys_str_mv AT ngovun lymphotoxinabandtumornecrosisfactorarerequiredforstromalcellexpressionofhomingchemokinesinbandtcellareasofthespleen
AT kornerheinrich lymphotoxinabandtumornecrosisfactorarerequiredforstromalcellexpressionofhomingchemokinesinbandtcellareasofthespleen
AT gunnmichaeld lymphotoxinabandtumornecrosisfactorarerequiredforstromalcellexpressionofhomingchemokinesinbandtcellareasofthespleen
AT schmidtkerstinn lymphotoxinabandtumornecrosisfactorarerequiredforstromalcellexpressionofhomingchemokinesinbandtcellareasofthespleen
AT seanrimintond lymphotoxinabandtumornecrosisfactorarerequiredforstromalcellexpressionofhomingchemokinesinbandtcellareasofthespleen
AT coopermaxd lymphotoxinabandtumornecrosisfactorarerequiredforstromalcellexpressionofhomingchemokinesinbandtcellareasofthespleen
AT browningjeffreyl lymphotoxinabandtumornecrosisfactorarerequiredforstromalcellexpressionofhomingchemokinesinbandtcellareasofthespleen
AT sedgwickjonathond lymphotoxinabandtumornecrosisfactorarerequiredforstromalcellexpressionofhomingchemokinesinbandtcellareasofthespleen
AT cysterjasong lymphotoxinabandtumornecrosisfactorarerequiredforstromalcellexpressionofhomingchemokinesinbandtcellareasofthespleen