NDLI: Ikaros-Notch axis in host hematopoietic cells regulates experimental graft-versus-host disease

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Ikaros-Notch axis in host hematopoietic cells regulates experimental graft-versus-host disease

Content Provider	Scilit
Author	Toubai, Tomomi Sun, Yaping Tawara, Isao Friedman, Ann Liu, Chen Evers, Rebecca Nieves, Evelyn Malter, Chelsea Chockley, Peter Maillard, Ivan Winandy, Susan Reddy, Pavan
Copyright Year	2011
Description	Host hematopoietically derived APCs play a vital role in the initiation of GVH responses. However, the APC autonomous molecular mechanisms that are critical for the induction of GVHD are not known. We report here that the Ikaros-Notch axis in host hematopoietically derived APCs regulates the severity of acute GVHD across multiple clinically relevant murine models of experimental bone marrow transplantation. In the present study, Ikaros deficiency (Ik−/−) limited to host hematopoietically derived APCs enhanced donor T-cell expansion and intensified acute GVHD, as determined by survival and other GVHD-specific parameters. The Ik−/− conventional CD8+ and CD8−CD11c+ dendritic cells (DCs), the most potent APCs, showed no increase in the expression of activation markers or in response to TLR stimulation compared with wild-type controls. However, Ik−/− DCs demonstrated an enhanced stimulation of allogeneic T cells. Deficiency of Ikaros in the conventional CD8+ and CD8−CD11c+ DCs was associated with an increase in Notch signaling, the blockade of which mitigated the enhanced in vitro and in vivo allostimulatory capacity. Therefore, the Ikaros-Notch axis is a novel pathway that modulates DC biology in general, and targeting this pathway in host hematopoietically derived APCs may reduce GVHD.
Related Links	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139384/pdf
Ending Page	204
Page Count	13
Starting Page	192
DOI	10.1182/blood-2010-12-324616
Journal	Blood
Issue Number	1
Volume Number	118
Language	English
Publisher	American Society of Hematology
Publisher Date	2011-07-07
Access Restriction	Open
Subject Keyword	Research and Experimental Medicine Hematopoietic Cells Host Hematopoietically Derived Apcs Gvhd Ikaros Notch Notch Axis Notch Signaling Bone Marrow Transplantation Journal: Blood (Vol- 21, Issue- 1)
Content Type	Text
Resource Type	Article

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