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
Copyright policy )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 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.
- Centenary Institute of Cancer Medicine and Cell Biology Australia
- Howard Hughes Medical Institute United States
- University of California, San Francisco United States
- UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- University of Alabama at Birmingham United States
Receptors, CXCR5, 570, Biomedical and clinical sciences, dendritic cell, Knockout, T-Lymphocytes, Immunology, Messenger, 610, lymphocyte, Medical and Health Sciences, follicle, follicular dendritic cell, Mice, Cell Movement, GTP-Binding Proteins, Receptors, 2.1 Biological and endogenous factors, Animals, RNA, Messenger, Aetiology, Receptors, Cytokine, lymphoid tissue, Cytokine, Lymphotoxin-alpha, In Situ Hybridization, Mice, Knockout, CXC, B-Lymphocytes, Biomedical and Clinical Sciences, Tumor Necrosis Factor-alpha, Inflammatory and immune system, Health sciences, Chemokine CXCL13, CXCR5, Gene Expression Regulation, Chemokine, RNA, Receptors, Chemokine, Chemokines, Cell Adhesion Molecules, Chemokines, CXC, Spleen
Receptors, CXCR5, 570, Biomedical and clinical sciences, dendritic cell, Knockout, T-Lymphocytes, Immunology, Messenger, 610, lymphocyte, Medical and Health Sciences, follicle, follicular dendritic cell, Mice, Cell Movement, GTP-Binding Proteins, Receptors, 2.1 Biological and endogenous factors, Animals, RNA, Messenger, Aetiology, Receptors, Cytokine, lymphoid tissue, Cytokine, Lymphotoxin-alpha, In Situ Hybridization, Mice, Knockout, CXC, B-Lymphocytes, Biomedical and Clinical Sciences, Tumor Necrosis Factor-alpha, Inflammatory and immune system, Health sciences, Chemokine CXCL13, CXCR5, Gene Expression Regulation, Chemokine, RNA, Receptors, Chemokine, Chemokines, Cell Adhesion Molecules, Chemokines, CXC, Spleen
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).526 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 1% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 0.1%
Citations provided by BIP!Popularity provided by BIP!