The role of IL-1beta in reduced IL-7 production by stromal and epithelial cells: a model for impaired T-cell numbers in the gut during HIV-1 infection.
OBJECTIVE
Interleukin (IL)-7 is a key cytokine in T-cell homeostasis. Stromal cells, intestinal epithelial cells and keratinocytes are known to produce this cytokine. The mechanisms and cellular factors regulating IL-7 production are still unclear. We assessed whether IL-1beta and interferon (IFN)-gamma, cytokines produced during inflammatory conditions, may impact on IL-7 production.


METHODS
We used human intestinal epithelial cells (DLD-1 cell line) and bone marrow stromal cells (HS27 cell line), known to produce IL-7; IL-7 production was evaluated at the mRNA and protein levels. To assess whether treatment of HS27 cells with IL-1beta and/or IFN-gamma leads to changes in the gene expression of cytokines, Toll-like receptors (TLRs) and chemokines, we analysed gene expression profiles using the whole-genome microarray Human Gene 1.0 ST.


RESULTS
We found that IFN-gamma enhanced the expression of IL-7 mRNA (P < 0.001) in both cell lines. IL-1beta treatment led to a significant down-regulation (P < 0.001) of IL-7 mRNA expression in both cell lines. The IL-7 concentration in supernatants collected from treated DLD-1 and HS27 cell cultures reflected the trend of IL-7 mRNA levels. The gene profiles revealed dramatic changes in expression of cytokines and their receptors (IL-7/IL-7R alpha; IL-1alpha,IL-1beta/IL-1R1; IFN-gamma/IFN-gammaR1), of IFN regulatory factors (IRF-1 and 2), of TLRs and of important chemo-attractants for T cells. The microarray results were verified by additional methods.


CONCLUSIONS
Our results are discussed in the setting of inflammation and T-cell survival in the gut compartment during HIV-1 infection where stromal and epithelial cells may produce factors that contribute to impaired IL-7 homeostasis and homing of T cells.
Thang
P H
PH
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Ruffin
N
N
Brodin
D
D
Rethi
B
B
Cam
P D
PD
Hien
N T
NT
Lopalco
L
L
Vivar
N
N
Chiodi
F
F
D017209:Apoptosis / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D018928:Immunity, Mucosal; D007371:Interferon-gamma / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology*; D015851:Interleukin-7 / Q000096:biosynthesis* / Q000235:genetics; D018448:Models, Immunological; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D019707:Receptors, Chemokine / Q000378:metabolism; D017154:Stromal Cells / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism
D016207:Cytokines; D053583:Interleukin-1beta; D015851:Interleukin-7; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D019014:fas Receptor; D007371:Interferon-gamma