TY - JOUR
T1 - Siglec-G-CD24 axis controls the severity of graft-versus-host disease in mice
AU - Toubai, Tomomi
AU - Hou, Guoqing
AU - Mathewson, Nathan
AU - Liu, Chen
AU - Wang, Ying
AU - Oravecz-Wilson, Katherine
AU - Cummings, Emily
AU - Rossi, Corinne
AU - Evers, Rebecca
AU - Sun, Yaping
AU - Wu, Julia
AU - Choi, Sung Won
AU - Fang, Dexing
AU - Zheng, Pan
AU - Liu, Yang
AU - Reddy, Pavan
PY - 2014/5/29
Y1 - 2014/5/29
N2 - Activation of sialic-acid - binding immunoglobulin-like lectin-G (Siglec-G) by non-infectious damage-associated molecular patterns controls innate immune responses. However, whether it also regulates T-cell - mediated adaptive immune responses is not known. Graft-versus-host reaction is a robust adaptive immune response caused by allogeneic hematopoietic cell transplantation that have been activated by antigen-presenting cells (APCs) in the context of damaged host tissues following allogeneic hematopoietic cell transplantation. The role of infectious and noninfectious pattern recognition receptor - mediated activation in the induction and aggravation of graft-versus-host disease (GVHD) is being increasingly appreciated. But the role of pathways that control innate immune responses to noninfectious stimuli in modulating GVHD has heretofore not been recognized. We report that Siglec-G expression on host APCs, specifically on hematopoietic cells, negatively regulates GVHD in multiple clinically relevant murine models. Mechanistic studies with various relevant Siglec-G and CD24 knockout mice and chimeric animals, along with rescue experiments with novel CD24 fusion protein demonstrate that enhancing the interaction between Siglec-G on host APCs with CD24 on donor T cells attenuates GVHD. Taken together, our data demonstrate that Siglec-G - CD24 axis, controls the severity ofGVHDand suggest that enhancing this interaction may represent a novel strategy for mitigating GVHD.
AB - Activation of sialic-acid - binding immunoglobulin-like lectin-G (Siglec-G) by non-infectious damage-associated molecular patterns controls innate immune responses. However, whether it also regulates T-cell - mediated adaptive immune responses is not known. Graft-versus-host reaction is a robust adaptive immune response caused by allogeneic hematopoietic cell transplantation that have been activated by antigen-presenting cells (APCs) in the context of damaged host tissues following allogeneic hematopoietic cell transplantation. The role of infectious and noninfectious pattern recognition receptor - mediated activation in the induction and aggravation of graft-versus-host disease (GVHD) is being increasingly appreciated. But the role of pathways that control innate immune responses to noninfectious stimuli in modulating GVHD has heretofore not been recognized. We report that Siglec-G expression on host APCs, specifically on hematopoietic cells, negatively regulates GVHD in multiple clinically relevant murine models. Mechanistic studies with various relevant Siglec-G and CD24 knockout mice and chimeric animals, along with rescue experiments with novel CD24 fusion protein demonstrate that enhancing the interaction between Siglec-G on host APCs with CD24 on donor T cells attenuates GVHD. Taken together, our data demonstrate that Siglec-G - CD24 axis, controls the severity ofGVHDand suggest that enhancing this interaction may represent a novel strategy for mitigating GVHD.
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U2 - 10.1182/blood-2013-12-545335
DO - 10.1182/blood-2013-12-545335
M3 - Article
C2 - 24695850
AN - SCOPUS:84901716156
SN - 0006-4971
VL - 123
SP - 3512
EP - 3523
JO - Blood
JF - Blood
IS - 22
ER -