Recent advances on cellular therapies and immune modulators for graft-versus-host disease

Filippini, Perla; Rutella, Sergio

doi:10.1586/1744666x.2014.955475

Cited by 8 publications

(6 citation statements)

References 120 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Treg adoptive cellular therapy has been shown to ameliorate autoimmune disease, graft rejection and GVHD. Translating adoptive tTreg therapy to humans has proceeded slowly due to challenges in maintaining high expression of Foxp3 in cultured cells, overall yield, and in vivo persistence of tTregs in GVHD patients 50 , 51 . In this study, we have shown that nanoparticle-mediated delivery of miR-142-3p antagomir to in vitro expanded tTreg is an easy and efficient way of overcoming these challenges, which may be useful in clinical applications.…”

Section: Discussionmentioning

confidence: 99%

miR-142-3p regulates autophagy by targeting ATG16L1 in thymic-derived regulatory T cell (tTreg)

Gao

Zhang

et al. 2018

Cell Death Dis

View full text Add to dashboard Cite

Thymic-derived regulatory T cell (tTreg) clinical trials show therapeutic promise in the prevention of acute graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation patients. However, strategies are needed to improve tTreg proliferative ability and survival as a means to improve tTreg therapy and reduce the requirement for producing large numbers of Treg cells for adoptive tTreg transfer. Autophagy is a self-degradative process for cytosolic components, which is involved in cells death, differentiation, lymphocyte homeostasis, and tTreg function. Studies have shown that mice with tTreg cells that have a disrupted autophagy process have defective tTreg cell generation and function, resulting in autoimmune disease and failed GVHD prevention by adoptively transferred tTreg cells. We found the attenuated autophagy status during ex vivo expansion, which leads us to determine whether tTreg cell survival could be augmented by miR-142-3p, the miRNA which is highly expressed in tTreg cells and potentially targets autophagy-related protein (ATG)-1, ATG16L1. We demonstrate that miR-142-3p downregulates ATG16L1 mRNA and production of ATG16L1, that has been linked to autoimmune diseases. Conversely, miR-142-3p knock-down improved tTreg cell expansion, survival and function in vitro and vivo. In aggregate, these studies provide a new approach that uses miR-142-3p knockdown to increase tTreg cell efficacy by increasing ATG16L1 mRNA and protein and the autophagy process.

show abstract

Section: Discussionmentioning

confidence: 99%

miR-142-3p regulates autophagy by targeting ATG16L1 in thymic-derived regulatory T cell (tTreg)

Gao

Zhang

et al. 2018

Cell Death Dis

View full text Add to dashboard Cite

show abstract

“…Translating adoptive tTreg therapy to humans has proceeded slowly because of challenges in maintaining a high expression of Foxp3 in cultured cells, overall yield, and in vivo persistence of tTregs in GVHD patients. 70,71 In this study, we have shown that nanoparticle-mediated delivery of miR-146b-5p antagomir to in vitro-expanded tTregs is an easy and efficient way of overcoming these challenges, which may be useful in clinical applications.…”

Section: Cd4mentioning

confidence: 97%

miR-146b antagomir–treated human Tregs acquire increased GVHD inhibitory potency

Hippen

Lemire

et al. 2016

Blood

View full text Add to dashboard Cite

show abstract

“…The pathogenesis of aGVHD is commonly considered to be immune‐mediated (Okamoto et al , ; Chao & Chen, ; Ferrara & Reddy, ; Sun et al , ; Petersdorf, ; Filippini & Rutella, ; Markey et al , ; Teshima et al , ). Corticosteroids are the standard first‐line therapy, achieving responses in approximately 25–40% of aGVHD patients, with clinically relevant improvement, defined as regression of skin rash or decrease in the volume of diarrhea and the extent of liver function abnormalities, in 40–50% of patients with grade II to IV aGVHD (Deeg, ).…”

mentioning

confidence: 99%

Impairment of bone marrow endothelial progenitor cells in acute graft‐versus‐host disease patients after allotransplant

et al. 2018

View full text Add to dashboard Cite

Graft-versus-host disease (GVHD) is a major complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT) that is frequently associated with bone marrow (BM) suppression, and clinical management is challenging. BM endothelial progenitor cells (EPCs) play crucial roles in the regulation of haematopoiesis and thrombopoiesis. However, little is known regarding the functional roles of BM EPCs in acute GVHD (aGVHD) patients. In the current prospective case-control study, reduced and dysfunctional BM EPCs, characterized by decreased migration and angiogenesis capacities and increased levels of reactive oxygen species (ROS) and apoptosis, were found in aGVHD patients compared with those without aGVHD. Moreover, lower frequency and increased levels of ROS, apoptosis and DNA damage, but reduced colony-forming unit-plating efficiency were found in BM CD34 + cells of aGVHD patients compared with those without aGVHD. The severity of aGVHD and GVHD-mediated cytopenia was associated with BM EPC impairment in aGVHD patients. In addition, the EPC impairment positively correlated with ROS level. Taken together, our results suggest that reduced and dysfunctional BM EPCs may be involved in the pathogenesis of aGVHD. Although these findings require validation, our data indicate that improvement of BM EPCs may represent a promising therapeutic approach for aGVHD patients.

show abstract

Recent advances on cellular therapies and immune modulators for graft-versus-host disease

Cited by 8 publications

References 120 publications

miR-142-3p regulates autophagy by targeting ATG16L1 in thymic-derived regulatory T cell (tTreg)

miR-142-3p regulates autophagy by targeting ATG16L1 in thymic-derived regulatory T cell (tTreg)

miR-146b antagomir–treated human Tregs acquire increased GVHD inhibitory potency

Impairment of bone marrow endothelial progenitor cells in acute graft‐versus‐host disease patients after allotransplant

Contact Info

Product

Resources

About