Abstract
Type I interferons have been typically studied for their effects in the context of bacterial or viral infections. However in this report, we provide evidence that Interferon-alpha (IFN-α) expressing cells are present in the thymus in the absence of infection. We show that pDC express the highest level of IFN-α and that MxA, which is exclusively expressed after engagement of the type I IFN receptor by IFN-α/β, is expressed in normal fetal and post-natal thymus, but not in the periphery. The highest level of MxA is expressed in mature thymocytes and pDC located in the medulla and at the cortico-medullary junction. The anti-microbial peptide LL-37, which is expressed in the thymus, when complexed with eukaryotic nucleic acids, induces the secretion of IFN-α by thymic pDC. This results in the upregulation of MxA expression in responsive thymocytes. We propose that the secretion of IFN-α in the thymus may function to regulate the rate of T cell development and modulate the requirements for the selection of developing T cells.
Highlights
Type I interferons (IFN) are immunomodulatory cytokines that function to alert cells to the presence of pathogens [1]
We show that the interferon induced protein Myxovirus resistance A (MxA) is constitutively expressed in post-natal and fetal thymus, but not in peripheral lymphoid tissues including fetal spleen and lymph nodes
We observed that the antimicrobial peptide LL-37 is expressed in the thymus, and that this in complex with eukaryotic DNA/RNA can stimulate thymic plasmacytoid dendritic cells (pDC) to express IFN-a in vitro
Summary
Type I interferons (IFN) are immunomodulatory cytokines that function to alert cells to the presence of pathogens [1]. IFN-a receptor signaling leads to phosphorylation of STAT1/2 and results in the expression of interferon regulatory factor 7 (IRF-7), required for the transcription of downstream ISG. MxA protein inhibits the viral life cycle at three distinct steps, including nucleocapsid transport to the nucleus [6], transcription of viral gene products [7], or viral assembly [8]. Expression of this particular ISG is tightly regulated and only expressed when IFN-a is secreted [9]. Expression of MxA has been widely utilized as a bio-marker for secreted IFN-a/b in both viral and bacterial infections [10,11,12]
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