Characterization of CD41 cells in the lymph node.

Lymph nodes (LNs) are the critical sites of immunity, and the stromal cells of LNs are crucial to their function. Our understanding of the stromal compartment of the LN has deepened recently with the characterization of nontraditional stromal cells. CD41 (integrin αIIb) is known to be expressed by platelets and hematolymphoid cells.

Target receptor identification and subsequent treatment of resected brain tumors with encapsulated and engineered allogeneic stem cells.

Cellular therapies offer a promising therapeutic strategy for the highly malignant brain tumor, glioblastoma (GBM). However, their clinical translation is limited by the lack of effective target identification and stringent testing in pre-clinical models that replicate standard treatment in GBM patients. In this study, we show the detection of cell surface death receptor (DR) target on CD146-enriched circulating tumor cells (CTC) captured from the blood of mice bearing GBM and patients diagnosed with GBM.

Characterization of Leptin Receptor Stromal Cells in Lymph Node.

Lymph node (LN)-resident stromal cells play an essential role in the proper functioning of LNs. The stromal compartment of the LN undergoes significant compensatory changes to produce a milieu amenable for regulation of the immune response. We have identified a distinct population of leptin receptor-expressing (LepR) stromal cells, located in the vicinity of the high endothelial venules (HEVs) and lymphatics.

ACTH treatment promotes murine cardiac allograft acceptance.

Heart transplantation is the optimal therapy for patients with end-stage heart disease, but its long-term outcome remains inadequate. Recent studies have highlighted the importance of the melanocortin receptors (MCRs) in inflammation, but how MCRs regulate the balance between alloreactive T cells and Tregs, and whether they impact chronic heart transplant rejection, is unknown. Here, we found that Tregs express MC2R, and MC2R expression was highest among all MCRs by Tregs.

Direct Tumor Killing and Immunotherapy through Anti-SerpinB9 Therapy.

Cancer therapies kill tumors either directly or indirectly by evoking immune responses and have been combined with varying levels of success. Here, we describe a paradigm to control cancer growth that is based on both direct tumor killing and the triggering of protective immunity. Genetic ablation of serine protease inhibitor SerpinB9 (Sb9) results in the death of tumor cells in a granzyme B (GrB)-dependent manner.

Cellular Mechanisms of Rejection of Optic and Sciatic Nerve Transplants: An Observational Study.

Background: Organ transplantation is a standard therapeutic strategy for irreversible organ damage, but the utility of nerve transplantation remains generally unexplored, despite its potential benefit to a large patient population. Here, we aimed to establish a feasible preclinical mouse model for understanding the cellular mechanisms behind the rejection of peripheral and optic nerves.

Methods: We performed syngenic and allogenic transplantation of optic and sciatic nerves in mice by inserting the nerve grafts inside the kidney capsule, and we assessed the allografts for signs of rejection through 14 d following transplantation.

Lymph node fibroblastic reticular cells deposit fibrosis-associated collagen following organ transplantation.

Although the immune response within draining lymph nodes (DLNs) has been studied for decades, how their stromal compartment contributes to this process remains to be fully explored. Here, we show that donor mast cells were prominent activators of collagen I deposition by fibroblastic reticular cells (FRCs) in DLNs shortly following transplantation. Serial analysis of the DLN indicated that the LN stroma did not return to its baseline microarchitecture following organ rejection and that the DLN contained significant fibrosis following repetitive organ transplants.

Nanodelivery of Mycophenolate Mofetil to the Organ Improves Transplant Vasculopathy.

Inflammation occurring within the transplanted organ from the time of harvest is an important stimulus of early alloimmune reactivity and promotes chronic allograft rejection. Chronic immune-mediated injury remains the primary obstacle to the long-term success of organ transplantation. However, organ transplantation represents a rare clinical setting in which the organ is accessible , providing an opportunity to use nanotechnology to deliver therapeutics directly to the graft.

Immune heterogeneity of head and tail pancreatic lymph nodes in non-obese diabetic mice.

The pancreatic lymph node is critical to the pathogenesis of autoimmune diabetes, as it constitutes the initial site for the priming of autoreactive T cells. In this study, we compared the histopathology of the head pancreatic lymph node (HPLN) to the tail pancreatic lymph node (TPLN) in NOD mice. HPLNs and TPLNs were harvested from 4 week-, 8 week-, and 12 week-old NOD mice, and their microvasculature, extracellular matrix, and immune cell subsets were characterized.

Anti-IL-6 eluting immunomodulatory biomaterials prolong skin allograft survival.

A primary goal in the management of burn wounds is early wound closure. The use of skin allografts represents a lifesaving strategy for severe burn patients, but their ultimate rejection limits their potential efficacy and utility. IL-6 is a major pleiotropic cytokine which critically links innate and adaptive immune responses.

Ectopic high endothelial venules in pancreatic ductal adenocarcinoma: A unique site for targeted delivery.

Background: Nanomedicine offers an excellent opportunity to tackle treatment-refractory malignancies by enhancing the delivery of therapeutics to the tumor site. High endothelial venules (HEVs) are found primarily in lymph nodes or formed de novo in peripheral tissues during inflammatory responses. They express peripheral node addressin (PNAd), which is recognized by the monoclonal antibody MECA79.

Targeted delivery of immune therapeutics to lymph nodes prolongs cardiac allograft survival.

The targeted delivery of therapeutic drugs to lymph nodes (LNs) provides an unprecedented opportunity to improve the outcomes of transplantation and immune-mediated diseases. The high endothelial venule is a specialized segment of LN vasculature that uniquely expresses peripheral node addressin (PNAd) molecules. PNAd is recognized by MECA79 mAb.

Repetitive ischemic injuries to the kidneys result in lymph node fibrosis and impaired healing.

The contribution of the kidney-draining lymph node (KLN) to the pathogenesis of ischemia-reperfusion injury (IRI) of the kidney and its subsequent recovery has not been explored in depth. In addition, the mechanism by which repetitive IRI contributes to renal fibrosis remains poorly understood. Herein, we have found that IRI of the kidney is associated with expansion of high endothelial venules (HEVs) and activation of fibroblastic reticular cells (FRCs) in the KLN, as demonstrated by significant expansion in the extracellular matrix.

Ischemia augments alloimmune injury through IL-6-driven CD4 alloreactivity.

Ischemia reperfusion injuries (IRI) are unavoidable in solid organ transplantation. IRI augments alloimmunity but the mechanisms involved are poorly understood. Herein, we examined the effect of IRI on antigen specific alloimmunity.

Regulation of T cell alloimmunity by PI3Kγ and PI3Kδ.

Phosphatidylinositol-3-kinases (PI3K) γ and δ are preferentially enriched in leukocytes, and defects in these signaling pathways have been shown to impair T cell activation. The effects of PI3Kγ and PI3Kδ on alloimmunity remain underexplored. Here, we show that both PI3Kγ and PI3Kδ mice receiving heart allografts have suppression of alloreactive T effector cells and delayed acute rejection.