During systemic immune responses, plasma blasts are generated in secondary lymphoid organs and migrate to the bone marrow, where they can become long-lived, being responsible for the maintenance of long-term antibody titers. Plasma blasts generated in mucosal immune responses of the small intestine home to the lamina propria (LP), producing mainly immunoglobulin A. The migration of these antibody-secreting cells is well characterized during acute immune responses. Less is known about their lifetime and contribution to the long-lived bone marrow compartment. Here we investigate the lifetime of plasma cells (PCs) and the relationship between the PC compartments of the gut and bone marrow after oral immunization. Our findings indicate that PCs in the LP can survive for extended time periods. PCs specific for orally administered antigens can be detected in the bone marrow for at least 9 months after immunization, indicating that the mucosal PC compartment can contribute to the long-lived PC pool in this organ, independent of the participation of splenic B cells. Our findings suggest that the compartmentalization between mucosal and systemic PC pools is less strict than previously thought. This may have implications for the development of vaccines as well as for autoantibody-mediated diseases.

This prospective study confirms a high incidence of fUTI after pediatric KTx, which is not restricted to patients with CAKUT; fUTIs have a negative impact on graft function during the infectious episode but not on 2-year graft outcome.

Application of mesenchymal stromal cells (MSC) has been proposed for solid organ transplantation based on their potent immunomodulatory effects. Since side effects from the injection of large cells cannot be excluded, the hypothesis rises that extracellular vesicles (EV) may cause immunomodulatory effects comparable to MSC without additional side effects. We used MSC-derived EV in a rat renal transplant model for acute rejection. We analysed peripheral blood leukocytes (PBL), kidney function, graft infiltrating cells, cytokines in the graft, and alloantibody development in animals without (allo) and with EV application (allo EV). There was no difference in kidney function and in the PBL subpopulation including Tregs between allo and allo EV. In the grafts T- and B-cell numbers were significantly higher and NK-cells lower in the allo EV kidneys compared to allo. TNF-α transcription was lower in allo EV grafts compared to allo; there was no difference regarding IL-10 and in the development of alloantibodies. In conclusion, the different cell infiltrates and cytokine transcription suggest distinct immunomodulatory properties of EV in allotransplantation. While the increased T- and B-cells in the allo EV grafts may represent a missing or negative effect on the adaptive immune system, EV seem to influence the innate immune system in a contrary fashion.

Idiopathic steroid-resistant nephrotic syndrome (SRNS) is most frequently characterized by focal segmental glomerulosclerosis (FSGS) but also other histological lesions, such as diffuse mesangial sclerosis. In the past two decades, a multitude of genetic causes of SRNS have been discovered raising the question of effective treatment in this cohort. Although no controlled studies are available, this review will discuss treatment options including pharmacologic interventions aiming at the attenuation of proteinuria in genetic causes of SRNS, such as inhibitors of the renin–angiotensin–aldosterone system and indomethacin. Also, the potential impact of other interventions to improve podocyte stability will be addressed. In this respect, the treatment with cyclosporine A (CsA) is of interest, since a podocyte stabilizing effect has been demonstrated in various experimental models. Although clinical response to CsA in children with genetic forms of SRNS is inferior to sporadic SRNS, some recent studies show that partial and even complete response can be achieved even in individual patients inherited forms of nephrotic syndrome. Ideally, improved pharmacologic and molecular approaches to induce partial or even complete remission will be available in the future, thus slowing or even preventing the progression toward end-stage renal disease.