Journal Article

Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks

Fletcher, Anne L, Turley, Shannon J, Knoblich, Konstantin, Hemler, Martin E, Tayalia, Prakriti, Lukacs-Kornek, Veronika, Carroll, Michael C, Chang, Sook Kyung, Astarita, Jillian, Gonzalez, Santiago F, Mooney, David J, Malhotra, Deepali, Brenner, Michael B, Elpek, Kutlu G

2012

Overview

The Immunological Genome Project aims to build a comprehensive database of gene-expression and gene-regulatory networks in the mouse immune system. Here Turley and colleagues analyze the transcriptomes of lymph-node stromal cells under steady-state and inflammatory conditions. Lymph node stromal cells (LNSCs) closely regulate immunity and self-tolerance, yet key aspects of their biology remain poorly elucidated. Here, comparative transcriptomic analyses of mouse LNSC subsets demonstrated the expression of important immune mediators, growth factors and previously unknown structural components. Pairwise analyses of ligands and cognate receptors across hematopoietic and stromal subsets suggested a complex web of crosstalk. Fibroblastic reticular cells (FRCs) showed enrichment for higher expression of genes relevant to cytokine signaling, relative to their expression in skin and thymic fibroblasts. LNSCs from inflamed lymph nodes upregulated expression of genes encoding chemokines and molecules involved in the acute-phase response and the antigen-processing and antigen-presentation machinery. Poorly studied podoplanin (gp38)-negative CD31 − LNSCs showed similarities to FRCs but lacked expression of interleukin 7 (IL-7) and were identified as myofibroblastic pericytes that expressed integrin α 7 . Together our data comprehensively describe the transcriptional characteristics of LNSC subsets.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/250/1620/1616 / 631/250/21 / 631/250/2504 / 631/61/212/2019 / Acute-Phase Reaction / Acute-Phase Reaction - immunology / Animals / Antigen Presentation / Antigen Presentation - immunology / Antigens, CD / Antigens, CD - immunology / Antigens, CD - metabolism / Biomedical and Life Sciences / Biomedicine / Cytokines / Cytokines - immunology / Cytokines - metabolism / Fibroblasts / Fibroblasts - immunology / Fibroblasts - metabolism / Gene Expression / Gene Expression - immunology / Genetic aspects / Growth factors / Homeostasis / Homeostasis - immunology / Immune response / Immunology / Infectious Diseases / Inflammation / Inflammation - genetics / Inflammation - immunology / Integrin alpha Chains / Integrin alpha Chains - immunology / Integrin alpha Chains - metabolism / Integrins / Interleukin-7 / Interleukin-7 - immunology / Interleukin-7 - metabolism / Life Sciences / Lymph Nodes / Lymph Nodes - cytology / Lymph Nodes - immunology / Membrane Glycoproteins / Membrane Glycoproteins - immunology / Membrane Glycoproteins - metabolism / Mice / Mice, Inbred C57BL / Pericytes / Pericytes - immunology / Pericytes - metabolism / Physiological aspects / Properties / resource / Self Tolerance / Self Tolerance - immunology / Stromal Cells / Stromal Cells - immunology / Stromal Cells - metabolism / Tissue Array Analysis / Tissue Array Analysis - methods / Transcriptome