Alarmins, sequestered self-molecules containing damage-associated molecular patterns, are released during tissue injury to drive innate immune cell proinflammatory responses. Whether endogenous negative regulators controlling early immune responses are also released at the site of injury is poorly understood. Herein, we establish that the stromal cell–derived alarmin interleukin 33 (IL-33) is a local factor that directly restricts the proinflammatory capacity of graft-infiltrating macrophages early after transplantation. By assessing heart transplant recipient samples and using a mouse heart transplant model, we establish that IL-33 is upregulated in allografts to limit chronic rejection. Mouse cardiac transplants lacking IL-33 displayed dramatically accelerated vascular occlusion and subsequent fibrosis, which was not due to altered systemic immune responses. Instead, a lack of graft IL-33 caused local augmentation of proinflammatory iNOS⁺ macrophages that accelerated graft loss. IL-33 facilitated a metabolic program in macrophages associated with reparative and regulatory functions, and local delivery of IL-33 prevented the chronic rejection of IL-33–deficient cardiac transplants. Therefore, IL-33 represents what we believe is a novel regulatory alarmin in transplantation that limits chronic rejection by restraining the local activation of proinflammatory macrophages. The local delivery of IL-33 in extracellular matrix–based materials may be a promising biologic for chronic rejection prophylaxis.

The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune receptor that affects cellular phenotypes by modulating phagocytosis and metabolism, promoting cell survival, and counteracting inflammation. Its role in renal injury, in particular, unilateral ureteral obstruction (UUO) or ischemia-reperfusion injury (IRI)-induced renal injury remains unclear. In our study, WT and Trem2^−/− mice were employed to evaluate the role of TREM2 in renal macrophage infiltration and tissue injury after UUO. Bone marrow-derived macrophages (BMDM) from both mouse genotypes were cultured and polarized for in vitro experiments. Next, the effects of TREM2 on renal injury and macrophage polarization in IRI mice were also explored. We found that TREM2 expression was upregulated in the obstructed kidneys. TREM2 deficiency exacerbated renal inflammation and fibrosis 3 and 7 days after UUO, in association with reduced macrophage infiltration. Trem2^−/− BMDM exhibited increased apoptosis and poorer survival compared with WT BMDM. Meanwhile, TREM2 deficiency augmented M1 and M2 polarization after UUO. Consistent with the in vivo observations, TREM2 deficiency led to increased polarization of BMDM towards the M1 proinflammatory phenotype. Mechanistically, TREM2 deficiency promoted M1 and M2 polarization via the JAK-STAT pathway in the presence of TGF-β1, thereby affecting cell survival by regulating mTOR signaling. Furthermore, cyclocreatine supplementation alleviated cell death caused by TREM2 deficiency. Additionally, we found that TREM2 deficiency promoted renal injury, fibrosis, and macrophage polarization in IRI mice. The current data suggest that TREM2 deficiency aggravates renal injury by promoting macrophage apoptosis and polarization via the JAK-STAT pathway. These findings have implications for the role of TREM2 in the regulation of renal injury that justify further evaluation.

Improved survival following organ transplantation has brought to the forefront some long-term complications, among which osteoporosis and associated fractures are the major ones that adversely affect the quality of life in recipients. The pathogenesis of osteoporosis in transplant recipients is complex and multifactorial which may be related to increased bone resorption, decreased bone formation, or both. Studies have shown that the preexisting underlying metabolic bone disorders and the use of immunosuppressive agents are the major risk factors for osteoporosis and fractures after organ transplantation. And rapid bone loss usually occurs in the first 6–12 months with a significant increase in fracture risk. This paper will provide an updated review on the possible pathogenesis of posttransplant osteoporosis and fractures, the natural history, and the current prevention and treatment strategies concerning different types of organ transplantation.

Since December 2019, the ongoing coronavirus disease 2019 (COVID-19) pandemic has significantly affected solid organ transplantation (SOT) worldwide and has become a threat to the lives of SOT recipients. Here, we have reviewed, condensed, and organized the available information on COVID-19 to provide recommendations to transplant healthcare workers. Our review of reported cases shows that the symptoms of SOT patients with COVID-19 are similar to those of the normal population, but their severity and outcomes are worse. Thus far, there is no evidence that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly causes permanent damage to kidney, liver, or heart allografts.

Background: Delayed graft function (DGF) is closely associated with the use of marginal donated kidneys due to deficits during transplantation and in recipients. We aimed to predict the incidence of DGF and evaluate its effect on graft survival.Methods: This retrospective study on kidney transplantation was conducted from January 1, 2018, to December 31, 2019, at the Second Xiangya Hospital of Central South University. We classified recipients whose operations were performed in different years into training and validation cohorts and used data from the training cohort to analyze predictors of DGF. A nomogram was then constructed to predict the likelihood of DGF based on these predictors.Results: The incidence rate of DGF was 16.92%. Binary logistic regression analysis showed correlations between the incidence of DGF and cold ischemic time (CIT), warm ischemic time (WIT), terminal serum creatine (Scr) concentration, duration of pretransplant dialysis, primary cause of donor death, and usage of LifePort. The internal accuracy of the nomogram was 83.12%. One-year graft survival rates were 93.59 and 99.74%, respectively, for the groups with and without DGF (P < 0.05).Conclusion: The nomogram established in this study showed good accuracy in predicting DGF after deceased donor kidney transplantation; additionally, DGF decreased one-year graft survival.

Neutrophils, which are traditionally regarded as a hallmark of inflammation, are also a member of the intratumoral immune cells. The roles of neutrophils in cancer development are diverse and undefined. So far, they are known to be involved in tumor initiation and tumor cell proliferation and metastasis. They show heterogeneity in both phenotypes and functions during early versus late stage of cancer development. Because they are also associated with the clinical outcomes of various types of solid tumors, cancer treatments that target neutrophils might be highly effective. In this review, we briefly cover the latest findings on the multiple roles of neutrophils in cancer development and point out the future directions as well.