Regeneration After Radiation- and Immune-Mediated Tissue Injury Is Not Enhanced by Type III Interferon Signaling
Fischer JC, Lin CC, Heidegger S, Wintges A, Schlapschy M, Beudert M, Combs SE, Bassermann F, Skerra A, Haas T, Poeck H (2019)
Publication Type: Journal article
Publication year: 2019
Journal
Book Volume: 103
Pages Range: 970-976
Journal Issue: 4
DOI: 10.1016/j.ijrobp.2018.11.038
Abstract
Purpose: Type I interferon (IFN-I) and interleukin (IL)-22 modulate regeneration of the thymus and intestinal epithelial cells (IECs) after cytotoxic stress such as irradiation. Radiation-induced damage to thymic tissues and IECs is a crucial aspect during the pathogenesis of inadequate immune reconstitution and acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with myeloablative total body irradiation (TBI), respectively. IL-22 and IFN-I reduce the severity of acute GVHD after allo-HSCT with myeloablative TBI. However, the role of biologically related type III interferon (IFN-III), also known as interferon lambda (IFN-λ) or IL-28, in this context is unclear. We therefore studied the role of the IFN-III pathway in thymic regeneration and GVHD after TBI and allo-HSCT. Methods and Materials: Cohoused wild-type (WT) and IFN-III receptor–deficient (IL-28 receptor alpha subunit–deficient/IL-28Ra –/– ) mice were analyzed in models of TBI-induced thymus damage and a model of GVHD after allo-HSCT with myeloablative TBI. PASylated IFN-III (PASylated IL-28A, XL-protein GmbH) was generated to prolong the plasma half-life of IFN-III. Pharmacologic activity and the effects of PASylated IL-28A on radiation-induced thymus damage and the course of GVHD after allo-HSCT with myeloablative TBI were tested. Results: The course and severity of GVHD after myeloablative TBI and allo-HSCT in IL-28Ra –/– mice was comparable to those in WT mice. Activation of the IFN-III pathway by PASylated IL-28A did not significantly modulate GVHD after allo-HSCT with TBI. Furthermore, IL28Ra –/– mice and WT mice showed similar thymus regeneration after radiation, which could also not be significantly modulated by IFN-III receptor engagement using PASylated IL-28A. Conclusions: We analyzed the role of IFN-III signaling during radiation-mediated acute tissue injury. Despite molecular and biologic homologies with IFN-I and IL-22, IFN-III signaling did not improve thymus regeneration after radiation or the course of GVHD after myeloablative TBI and allo-HSCT.
Involved external institutions
Germany (DE)How to cite
APA:
Fischer, J.C., Lin, C.-C., Heidegger, S., Wintges, A., Schlapschy, M., Beudert, M.,... Poeck, H. (2019). Regeneration After Radiation- and Immune-Mediated Tissue Injury Is Not Enhanced by Type III Interferon Signaling. International Journal of Radiation Oncology Biology Physics, 103(4), 970-976. https://doi.org/10.1016/j.ijrobp.2018.11.038
MLA:
Fischer, Julius C., et al. "Regeneration After Radiation- and Immune-Mediated Tissue Injury Is Not Enhanced by Type III Interferon Signaling." International Journal of Radiation Oncology Biology Physics 103.4 (2019): 970-976.
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