Toll-like receptor 2 deficiency promotes the generation of alloreactive Th17 cells after cardiac transplantation in mice

Li, Lingyun; Chen, Xiangyu; Zhang, Yuanyue; Li, Qirui; Chen, Qi; Fei, Xiaoyuan; Zheng, Fang; Gong, Feili; Fang, Min

doi:10.1016/j.cellimm.2019.02.005

Cited by 5 publications

(3 citation statements)

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“…This is in line with earlier studies showing similar findings in kidney transplantation ( 143 , 144 ). A recent study using TLR2-deficient mice on the other hand showed poor graft survival time, due to increased immune cell infiltration and enhanced pro-inflammatory Th17 cell responses ( 148 ). OPN-301 was not tested in models of HTx but was studied in a mouse model of renal transplantation, where it was administered after 30 min of cold ischemia prior to reperfusion.…”

Section: Pattern Recognition Receptors Related To Myocardial Ischemiamentioning

confidence: 99%

Damage-Associated Molecular Patterns in Myocardial Infarction and Heart Transplantation: The Road to Translational Success

et al. 2020

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In the setting of myocardial infarction (MI), ischemia reperfusion injury (IRI) occurs due to occlusion (ischemia) and subsequent re-establishment of blood flow (reperfusion) of a coronary artery. A similar phenomenon is observed in heart transplantation (HTx) when, after cold storage, the donor heart is connected to the recipient’s circulation. Although reperfusion is essential for the survival of cardiomyocytes, it paradoxically leads to additional myocardial damage in experimental MI and HTx models. Damage (or danger)-associated molecular patterns (DAMPs) are endogenous molecules released after cellular damage or stress such as myocardial IRI. DAMPs activate pattern recognition receptors (PRRs), and set in motion a complex signaling cascade resulting in the release of cytokines and a profound inflammatory reaction. This inflammatory response is thought to function as a double-edged sword. Although it enables removal of cell debris and promotes wound healing, DAMP mediated signalling can also exacerbate the inflammatory state in a disproportional matter, thereby leading to additional tissue damage. Upon MI, this leads to expansion of the infarcted area and deterioration of cardiac function in preclinical models. Eventually this culminates in adverse myocardial remodeling; a process that leads to increased myocardial fibrosis, gradual further loss of cardiomyocytes, left ventricular dilation and heart failure. Upon HTx, DAMPs aggravate ischemic damage, which results in more pronounced reperfusion injury that impacts cardiac function and increases the occurrence of primary graft dysfunction and graft rejection via cytokine release, cardiac edema, enhanced myocardial/endothelial damage and allograft fibrosis. Therapies targeting DAMPs or PRRs have predominantly been investigated in experimental models and are potentially cardioprotective. To date, however, none of these interventions have reached the clinical arena. In this review we summarize the current evidence of involvement of DAMPs and PRRs in the inflammatory response after MI and HTx. Furthermore, we will discuss various current therapeutic approaches targeting this complex interplay and provide possible reasons why clinical translation still fails.

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Section: Pattern Recognition Receptors Related To Myocardial Ischemiamentioning

confidence: 99%

Damage-Associated Molecular Patterns in Myocardial Infarction and Heart Transplantation: The Road to Translational Success

et al. 2020

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“…Previous studies have demonstrated that CD4 + IL-17 + cells constitute a subset of donor-reactive T cells and make critical contributions to allograft rejection ( 122 , 123 ). Similarly, alloreactive Tregs are crucial mediators of the tolerogenic response following transplantation ( 124 , 125 ).…”

Section: Discussionmentioning

confidence: 99%

ACTH treatment promotes murine cardiac allograft acceptance

Zhao¹,

Jiang²,

Uehara³

et al. 2021

JCI Insight

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“…143,144 A recent study using TLR2-deficient mice on the other hand showed poor graft survival time, due to increased immune cell infiltration and enhanced pro-inflammatory Th17 cell responses. 148 OPN-301 was not tested in models of HTx but was studied in a mouse model of renal transplantation, where it was administered after 30 min of cold ischemia prior to reperfusion. This treatment significantly improved kidney function after 6 days of transplantation based on blood urea nitrogen levels, which correlated with preserved tubular structure in mice that were treated with OPN-301.…”

Section: Experimental Therapeuticsmentioning

confidence: 99%

Coronary Artery Disease Inflammatory Pathways and Interventions

Silvis¹

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Toll-like receptor 2 deficiency promotes the generation of alloreactive Th17 cells after cardiac transplantation in mice

Cited by 5 publications

References 50 publications

Damage-Associated Molecular Patterns in Myocardial Infarction and Heart Transplantation: The Road to Translational Success

Damage-Associated Molecular Patterns in Myocardial Infarction and Heart Transplantation: The Road to Translational Success

ACTH treatment promotes murine cardiac allograft acceptance

Coronary Artery Disease Inflammatory Pathways and Interventions

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