The microbiome and the immune system are known to work in conjunction to modulate the clearance of pathogens and tolerance of beneficial microbes. A growing area of research seeks to study the potential extent of the involvement of the microbiome in modulating and supporting the immune system during acute allograft rejection. It has been hypothesized that the localized microbiota in each organ produce metabolites that instigate inflammatory immune responses, but whether microbiota interactions precipitate acute allograft rejection is unknown. Therefore, this study focuses on microbiome shifts in the gut and kidney after inducing acute renal transplant rejection in order to implicate gut dysbiosis as a precursor or supporter of allograft rejection. This study also subsequently explores the use of an immune-modulating protein in order to determine differences in the outcome of transplant rejection and potential differences in intestinal microbial load. This experiment sought to induce rejection in BALB/c mice through the use of C57BL/6 mouse renal slivers. Microbiome abundance was analyzed in all experimental groups. Understanding the role of the microbiome in transplant rejection has vast clinical implications and has the potential to enhance pre- and post-operative treatment, and immune management and quality of life following organ transplant.

The metastatic activity of breast carcinomas results from complex genetic changes in epithelial tumor cells and accounts for 90% of deaths in affected patients. Although the invasion of the local lymphatic vessels and veins by malignant breast tumor cells and their subsequent metastasis to the lung, has been recognized, the mechanisms behind the metastatic activity of breast tumor cells to other distal organs and the pathogenesis of metastatic cancer are not well understood. In this study, we utilized derivatives of the well-established and highly metastatic triple negative breast cancer (TNBC) cell line MDA-MB-231 (MDA-231) to study breast tumor metastasis in a mouse model. These MDA-231 derivatives had depleted expression of Kaiso, a POZ-ZF transcription factor that is highly expressed in malignant, triple negative breast cancers. We previously reported that Kaiso depletion attenuates the metastasis of xenografted MDA-231 cells. Herein, we describe the pathological features of the metastatic activity of parental (Kaiso^positive) versus Kaiso^depleted MDA-231 cells. Both Kaiso^positive and Kaiso^depleted MDA-231 cells metastasized from the original tumor in the mammary fat pad to the lung. However, while Kaiso^positive cells formed large masses in the lung parenchyma, invaded large pulmonary blood vessels and formed secondary metastases and large tumors in the distal organs, Kaiso^depleted cells metastasized only to the lung where they formed small metastatic lesions. Importantly, intravascular invasion and secondary metastases in distal organs were not observed in mice xenografted with Kaiso^depleted cells. It thus appears that the lung may constitute a barrier for less invasive breast tumors such as the Kaiso^depleted TNBC cells; this barrier may limit tumor growth and prevents Kaiso^depleted TNBC cells from invading the pulmonary blood vessels and forming secondary metastases in distal organs.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease resulting in widespread inflammation of various organ tissues including the lung, heart, kidneys, brain, joints, vasculature, and more. Systemic Lupus Erythematosus (SLE) has at present no cure and therefore, treatments focus on improving quality of life by targeting flare-ups of inflammation (6). Diffuse Alveolar Hemorrhage (DAH) is a rare complication of SLE affecting 1-5% of people diagnosed with SLE. DAH is characterized by bleeding into the lung alveolar spaces and is associated with inflammation, potentially caused by infections and injuries. While the prevalence of DAH is low, the mortality rate is high at 50-80% (5). DAH has no proven effective treatment and many treatments used have severe side effects. Serp-1 is a Myxomavirus derived immune modulating serine protease inhibitor, a serpin, with proven efficacy in a wide range of inflammation-associated disorders (1). Due to the efficacy of Serp-1 in reducing arterial inflammation and lung consolidation in mouse herpes virus infections, Serp-1 treatment in a mouse model of pristane-induced DAH was investigated. Multiple groups were tested including mouse models that were not given pristane as well as mice with pristane-induced DAH treated with saline control, wild-type unmodified Serp-1, and a polyethylene glycol-modified variant of Serp-1 termed PEGSerp-1.

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is an immune disorder that causes chronic inflammation of the gastrointestinal tract. There is an unmet need for effective pharmacological treatments as current standard therapies including aspirin derivatives and corticosteroids often fail to control the disease. For a significant portion, 30% or more, of patients, surgical removal of the affected bowel is required at some point in their disease course to address complications of bleeding, infections with sepsis, toxic megacolon among many others. There are also associated severe complications involving many other organs due to the underlying immune mediated reactions. In this study, PEGylated Serp-1 (PEGSerp-1) a modified Myxomavirus-derived serine protease inhibitor that binds and inhibits serine proteases in the coagulation and complement cascades, is evaluated in a pre-clinical model of IBD. Experimental colitis was induced in male C57BL/6J mice by oral administration of dextran sulfate sodium (DSS). In mice with acute colitis induced by exposure to 5% DSS for 6 days, daily treatment with PEGSerp-1 significantly improved survival. When initiation of treatment was delayed by 7 days in this acute colitis model, PEGSerp-1 treatment improved markers of disease severity and significantly reduced inflammation in the colon. PEGSerp-1 is an effective treatment of acute DSS-induced colitis when used as a preventative or delayed treatment.