The role of IL-1β in reduced IL-7 production by stromal and epithelial cells: A model for impaired T-cell numbers in the gut during HIV-1 infection

P. H. Thang, N. Ruffin, D. Brodin, B. Rethi, P. D. Cam, N. T. Hien, L. Lopalco, N. Vivar, F. Chiodi

Research output: Contribution to journalArticle

Abstract

Abstract. Thang PH, Ruffin N, Brodin D, Rethi B, Cam PD, Hien NT, Lopalco L, Vivar N, Chiodi F (Karolinska Institutet, Stockholm, Sweden; National Institute of Hygiene and Epidemiology, Hanoi, Vietnam; San Raffaele Scientific Institute, Milan, Italy). The role of IL-1β in reduced IL-7 production by stromal and epithelial cells: a model for impaired T-cell numbers in the gut during HIV-1 infection. J Intern Med 2010; 268: 181-193. Objectives. 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-1β and interferon (IFN)-γ, cytokines produced during inflammatory conditions, may impact on IL-7 production. Design. 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-1β and/or IFN-γ 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-γ enhanced the expression of IL-7 mRNA (P <0.001) in both cell lines. IL-1β 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-7Rα; IL-1α,IL-1β/IL-1R1; IFN-γ/IFN-γR1), 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.

Original languageEnglish
Pages (from-to)181-193
Number of pages13
JournalJournal of Internal Medicine
Volume268
Issue number2
DOIs
Publication statusPublished - Aug 2010

    Fingerprint

Keywords

  • apoptosis
  • gene profile
  • HIV
  • IL-1β
  • IL-7
  • T cells

ASJC Scopus subject areas

  • Internal Medicine

Cite this