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
Book Volume: 103
Pages Range: 970-976
Journal Issue: 4
DOI: 10.1016/j.ijrobp.2018.11.038
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.
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.
BibTeX: Download