Recipient Myd88 Deficiency Promotes Spontaneous Resolution of Kidney Allograft Rejection

Lerret, Nadine M.; Li, Ting; Wang, Jiao Jing; Kang, Hee Kap; Wang, Sheng; Wang, Xueqiong; Jie, Chunfa; Kanwar, Yashpal S.; Abécassis, Michaël; Luo, Xunrong; Zhang, Zheng

doi:10.1681/asn.2014080813

Cited by 15 publications

(16 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, activins have been shown to induce high‐mobility group box‐1 production, which is a central DAMP initiating the TLR signaling and innate immune response . In experimental kidney transplantation, impaired TLR signaling increases allograft survival . Thus, inhibition of the innate immune response might be beneficial in the transplant setting.…”

Section: Discussionmentioning

confidence: 99%

Activin inhibition limits early innate immune response in rat kidney allografts-a pilot study

et al. 2016

View full text Add to dashboard Cite

SUMMARYActivins are members of the transforming growth factor-beta (TGF-b) superfamily of cytokines. They play critical roles in the onset of acute and chronic inflammatory responses. The aim of this study was to investigate how activin inhibition affects acute kidney injury and inflammation after transplantation. The study was carried out in kidney transplantation and renal ischemia-reperfusion models in the rat. Soluble activin type 2 receptor (sActRIIB-Fc) was used to inhibit activin signaling. Transplantation groups were as follows: (i) cyclosporine A (CsA) (ii) CsA + sActRIIB-Fc, (iii) CsA+ inactive protein control Fc-G1. IRI groups were as follows: (i) no treatment, (ii) sActRIIB-Fc. Serum activin B concentration was significantly elevated after transplantation and IRI, whereas activin A was produced locally in renal allografts. Activin inhibition efficiently limited neutrophil, macrophage, and dendritic cell infiltration to the allografts measured 72 h after transplantation. In addition, sActRIIB-Fc treatment modulated serum cytokine response after transplantation and reduced the early accumulation of fibroblasts in the graft interstitium. In conclusion activin inhibition reduces the innate immune response early after renal transplantation in the rat. It also limits the accumulation of fibroblasts in the graft suggesting that activins may be involved in the fibrogenic signaling already early after kidney transplantation.

show abstract

Section: Discussionmentioning

confidence: 99%

Activin inhibition limits early innate immune response in rat kidney allografts-a pilot study

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Donor animals received CD47 antibody or PBS 3 hours before kidney harvest. Serum urea and creatinine were determined via the VetScan i-STAT 1 (Abaxis, Union City, CA), as published [50][51][52]. Statistical analysis Statistical analyses were performed using GraphPad Prism software (La Jolla, CA).…”

mentioning

confidence: 99%

CD47 regulates renal tubular epithelial cell self-renewal and proliferation following renal ischemia reperfusion

Rogers

Zhang

Wang

et al. 2016

Kidney International

Self Cite

View full text Add to dashboard Cite

Defects in renal tubular epithelial cell repair contribute to renal ischemia reperfusion injury, cause acute kidney damage, and promote chronic renal disease. The matricellular protein thrombospondin-1 and its receptor CD47 are involved in experimental renal ischemia reperfusion injury, although the role of this interaction in renal recovery is unknown. We found upregulation of self-renewal genes (transcription factors Oct4, Sox2, Klf4 and cMyc) in the kidney of CD47(-/-) mice after ischemia reperfusion injury. Wild-type animals had minimal self-renewal gene expression, both before and after injury. Suggestive of cell autonomy, CD47(-/-) renal tubular epithelial cells were found to increase expression of the self-renewal genes. This correlated with enhanced proliferative capacity compared with cells from wild-type mice. Exogenous thrombospondin-1 inhibited self-renewal gene expression in renal tubular epithelial cells from wild-type but not CD47(-/-) mice, and this was associated with decreased proliferation. Treatment of renal tubular epithelial cells with a CD47 blocking antibody or CD47-targeting small interfering RNA increased expression of some self-renewal transcription factors and promoted cell proliferation. In a syngeneic kidney transplant model, treatment with a CD47 blocking antibody increased self-renewal transcription factor expression, decreased tissue damage, and improved renal function compared with that in control mice. Thus, thrombospondin-1 via CD47 inhibits renal tubular epithelial cell recovery after ischemia reperfusion injury through inhibition of proliferation/self-renewal.

show abstract

“…Bilaterally nephrectomized naive B6 recipients (RÀ) were transplanted with a fully MHC-mismatch life-supporting kidney from BALB/c donors. 30 Donor BALB/c mice were latently infected with the MCMV strain Dm157 (10 8 pfu) 3-4 months before being used as donors for kidney transplantation (Dþ). 8 Recipients were either treated with indefinite immunosuppression (IS, regimen detailed in the Methods section) or tolerized with donor ECDI-SP (Tol).…”

Section: Transplantation Tolerance Induced By Donor Ecdi-sp Infusionsmentioning

confidence: 99%

Murine cytomegalovirus dissemination but not reactivation in donor-positive/recipient-negative allogeneic kidney transplantation can be effectively prevented by transplant immune tolerance

Dangi

Lee

et al. 2020

Kidney International

Self Cite

View full text Add to dashboard Cite

C ytomegalovirus (CMV) infection after transplantation in immunosuppressed recipients is common 1 and is often associated with an increased risk for acute and chronic allograft rejection. 2 The risk of CMV diseases is known to be the highest amongst CMV seronegative recipients (RÀ) receiving an organ from CMV seropositive donors (Dþ). 3,4 However, the mechanism of CMV reactivation and subsequent dissemination in such Dþ to RÀ combination is poorly understood. 5 Previously, it has been shown that after transplantation a multitude of systemically released inflammatory cytokines can promote CMV viral reactivation. 6-9 In addition, in vitro studies demonstrate that inflammatory mediators such as interleukins-6, tumor necrosis factor-a, or prostaglandin E2 can activate nuclear factor kB and

show abstract

Recipient Myd88 Deficiency Promotes Spontaneous Resolution of Kidney Allograft Rejection

Cited by 15 publications

References 55 publications

Activin inhibition limits early innate immune response in rat kidney allografts-a pilot study

Activin inhibition limits early innate immune response in rat kidney allografts-a pilot study

CD47 regulates renal tubular epithelial cell self-renewal and proliferation following renal ischemia reperfusion

Murine cytomegalovirus dissemination but not reactivation in donor-positive/recipient-negative allogeneic kidney transplantation can be effectively prevented by transplant immune tolerance

Contact Info

Product

Resources

About