Co-stimulation remains a target for transplantation and blocking therapeutics are available. An exciting negative co-stimulatory pathway may for the first time be directly amenable to targeting to inhibit the immune response.

Many studies have shown that IL-6 plays a significant role in defining the immune/alloimmune response. New therapies targeting pro-inflammatory cytokines are now available for the treatment of rheumatoid arthritis. Blockade of IL-6, Th17 related and other cytokines may not only decrease the pro-inflammatory response, but more importantly may favor a regulatory T cell response and thus potentially influence long-term allograft survival.

Ischemia/reperfusion injury (IRI) is an important component of organ dysfunction after transplantation. One of the consequences of IRI is activation of the innate immune response. Danger signals released by the damaged cells interact with membrane receptors to ultimately enhance the inflammatory response. Dr. Bonventre will discuss the role of KIM-1/TIM-1 on epithelial cells in down-regulating the innate immune response through NF-kB, and increasing autophagy and pro-tolerogenic MHC expression in the early phases of injury. Often IRI and associated acute kidney injury leads to chronic kidney disease. Prolonged expression of KIM-1/TIM-1 leads to a maladaptive response resulting in persistent tubular injury and a senescent secretory profibrotic phenotype.

Necroptosis is a newly described form of necrotic cell death induced under conditions where apoptosis was prevented. Necroptotic cell death is characterized by the same morphological features as unregulated necrotic death and induces intense inflammation. A new class of therapeutics called necrostatins can block this. New necrostatins, necrostatin-3 and necrostatin-5, target the RIP1 kinase step in the necroptosis pathway, but through mechanisms distinct from that of the original necrostatin-1. As a class, these new therapeutics have not been tested in transplantation but may hold a key position in blocking organ injury through control of necrosis. Understanding the basic biology of programmed necrosis in organ injury and applying these new therapeutics represent a potentially huge paradigm shift in managing organ injury, donor preservation and transplant survival.

Rapid and inexpensive nucleic acid sequencing technologies and advances in Mass Spectroscopy, as well as an appreciation for the role that bacteria, viruses, and fungi play in human health, have fueled multi-omics studies. In this talk, Dr. Fouts will describe the technologies currently being used to characterize the microbiome, what questions can be asked, the challenges being faced, and how microbiome studies can be translated into the clinic.

The talk will discuss the microbiome in the urine in kidney transplant patients. The focus will be primarily on viruses (including BK), with some discussion of bacteria.

The composition and function of the microbial communities within the body can influence the innate and adaptive arms of our immune system. A better understanding of the microbiome is radically redefining the idea of self vs. non-self and the not always symbiotic relationship between the microbiome and the immune response leading to potential for collateral damage to the allograft. Is it feasible to change your microbiome and is this most amenable to change by probiotics, diet, or fecal transplantation?

Organ senescence may contribute to premature organ failure but is difficult to assess and perhaps not yet possible to control. What are the lessons from pathology and molecular diagnostics that can help us? Is donor age or biological age the central and only variable for risk or are there markers that can guide us as to which organs are at greatest risk, for selection of recipients and for selection of immunosuppressive drugs?