Abstract
Signaling through the IL-1-receptor type 1 (IL-1R1), IL-1 is required for initiation and maintenance of diverse activities of the immune system. A second receptor, IL-1R2, blocks IL-1 signal transduction. We studied expression of IL-1beta, IL-1R1, and IL-1R2 in 17 Hodgkin lymphomas (HL) by in situ hybridization (ISH). IL-1beta expressing cells, morphologically consistent with endothelial cells and fibroblasts, occurred in all HL tissues with elevated transcript levels in areas of active fibrosis. Hodgkin and Reed-Sternberg (HRS) cells of all cases expressed low IL-1R1 transcript levels in some tumor cells, and high levels of IL-1R2 in large proportions of HRS cells. Only few bystander cells showed low levels of IL-1R1 and IL-1R2 RNA. Supernatants of 4 out of 7 HL-derived cell lines contained soluble IL-1R2 protein at high levels. HL patient sera carried variably amounts of IL-1R2 protein with significantly increased titers in patients with active disease compared to patients in complete remission and control individuals without HL. Western blots and co-immunoprecipitations showed binding of the IL-1R2 to the intracellular IL-1R-accessory protein (IL-1IRAcP). These data suggest functions of the IL-1R2 as a „decoy-receptor” sequestrating paracrine IL-1 extracellularly and intracellularly by engaging IL-1IRAcP, thus depriving IL1-R1 molecules of their extracellular and intracellular ligands. Expression of IL1-R2 by HRS cells seems to contribute to local and systemic modulation of immune function in HL.
Highlights
Hodgkin lymphoma (HL) is characterized by a paucity of neoplastic Hodgkin- and Reed-Sternberg (HRS) cells, embedded in a variably composed reactive cellular infiltrate
Heparin-plasma from 20 patients treated in our department within the studies of the German Hodgkin Lymphoma Study Group were available to Enzyme-linked immunosorbant assay (ELISA) studies with HL in complete remission (CR) and 18 patients with active disease present (DP; NSHL or MCHL, no further selection)
Exploring the potential role of the IL-1 network in HL, we studied expression of IL-1beta, IL-1-receptor type 1 (IL-1R1), and IL-1R2
Summary
Hodgkin lymphoma (HL) is characterized by a paucity of neoplastic Hodgkin- and Reed-Sternberg (HRS) cells, embedded in a variably composed reactive cellular infiltrate. Many of the distinct clinical and morphological features of HL, such as B-symptoms and the cellular composition of the reactive infiltrate, are thought to be related to a quantitatively and qualitatively abnormal expression of cytokines in HL lesions [2,3,4,5]. Some cytokines have a potential to influence immune reactions and may be responsible for the escape of HRS cells from T cell cytotoxicity [6]. PLOS ONE | DOI:10.1371/journal.pone.0138747 September 25, 2015
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