Tissue-specific function of lymph node fibroblastic reticulum cells.
OBJECTIVE
We present the first characterization of the cytokine expression pattern of lymph node fibroblastic reticulum cells (FRC), which are the stromal cells responsible for maintaining the highly structured nodal reticular fiber framework.


METHODS
Microarray expression profiles of cultured nodal FRC and dermal fibroblasts (DF) were compared as well as their response to TNF, IL-4, IL-6 and IL-13, cytokines responsible for intranodal stromal activation.


RESULTS
Hierarchical clustering of FRC and DF short-term culture samples revealed genes that were differentially expressed in FRC and DF. Identified differently regulated genes were confirmed by RNase protection analysis, PCR or immunohistochemistry. At earlier culture time points, FRC showed higher levels of several chemokines, including CCL2/MCP-1, and cytokines, e.g. IL-6, whereas several genes related to the production of extracellular matrix and angiogenesis were preferentially expressed in early DF cultures. By 60 days in culture, FRC and DF showed similar expression patterns consistent with homogenization of specialized stromal subsets. FRC and DF showed nearly identical transcriptional responses to exogenous TNF stimulation.


CONCLUSIONS
Cultured FRC showed an overall transcriptional profile similar to cultured DF, including parallel responsiveness to TNF, but with differences in the expression of chemotactic chemokines, which reflect their biological roles.
Vega
Francisco
F
Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Coombes
Kevin R
KR
Thomazy
Vilmos A
VA
Patel
Kaushali
K
Lang
Wenhua
W
Jones
Dan
D
D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D016207:Cytokines / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology*; D020411:Oligonucleotide Array Sequence Analysis; D012155:Reticulin / Q000502:physiology; D012867:Skin / Q000166:cytology; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C526317:CCN2 protein, human; D018925:Chemokines; D016207:Cytokines; D017874:Immediate-Early Proteins; D019012:Integrin beta1; D036341:Intercellular Signaling Peptides and Proteins; D012155:Reticulin; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D014409:Tumor Necrosis Factor-alpha; D055513:Connective Tissue Growth Factor