Knockout strainsCD11c-DTA (25) Irf8 2/2 ; Id2 2/2 ; Nfil3 2/2 ; Batf3 2/2 ; CD11c-Irf8 2/2 ; Ztbt46-Irf8 2/2 ; Xcr1-DTA; CD11c-Bcl6 2/2 (26-33) huLangerin-DTA; CD11c-Sirpa 2/2 ; CD11c-Cd47 2/2 ; CD11c-Notch2 2/2 ; Csf2r 2/2 ;Csf2 2/2 ; CD11c-Irf4 2/2 ; CD11c-Klf4 2/2 ; CD11c-Prdm1 2/2 ; CD11c-Tgfbr1 2/2 (11, 22, 23, 33-38) Inducible knockout strains CD11c-DTR; Zbtb46-DTR; Zbtb46 LSL-DTR Csf1r-Cre (5, 19, 39, 40) Clec9a-DTR; Xcr1-DTR (41-43) Clec4a4-DTR (42) Cre strains CD11c-Cre; Zbtb46-Cre (44, 45) Clec9a-Cre; Xcr1-Cre; Karma-Cre (31, 46, 47) huLangerin-Cre (48) Reporter strains CD11c-eYFP; Zbtb46-GFP (40, 49) Xcr1-Venus; Id2-GFP (43, 50) huLangerin-Cre 3 Rosa26-Stop fl/fl -YFP (48) aNote that in the case of the intestine, these examples of cDC2 deletion/depletion only pertain to CD103 + CD11b + cDC2 (subset 1). For CD103 2 CD11b + cDC2 (subset 2), Csf1r 2/2 mice may be used (34), as well as CD11c-Irf4 2/2 mice (partial depletion) (23).

No abstract

Redundant mechanisms support immunoglobulin A (IgA) responses to intestinal antigens. These include multiple priming sites [mesenteric lymph nodes (MLNs), Peyer’s patches, and isolated lymphoid follicles] and various cytokines that promote class switch to IgA, even in the absence of T cells. Despite these backup mechanisms, vaccination against enteric pathogens such as rotavirus has limited success in some populations. Genetic and environmental signals experienced during early life are known to influence mucosal immunity, yet the mechanisms for how these exposures operate remain unclear. Here, we used rotavirus infection to follow antigen-specific IgA responses through time and in different gut compartments. Using genetic and pharmacological approaches, we tested the role of the lymphotoxin (LT) pathway—known to support IgA responses—at different developmental stages. We found that LT-β receptor (LTβR) signaling in early life programs intestinal IgA responses in adulthood by affecting antibody class switch recombination to IgA and subsequent generation of IgA antibody-secreting cells within an intact MLN. In addition, early-life LTβR signaling dictates the phenotype and function of MLN stromal cells to support IgA responses in the adult. Collectively, our studies uncover new mechanistic insights into how early-life LTβR signaling affects mucosal immune responses during adulthood.

Both authors contributed equally to this paper.Fibrinogen-like protein 2 (FGL2) is an immunomodulatory protein that is expressed by regulatory T cells (Tregs). The objective of this study was to determine if recombinant FGL2 (rFGL2) treatment or constitutive FGL2 overexpression could promote transplant tolerance in mice. Although rFGL2 treatment prevented rejection of fully mismatched cardiac allografts, all grafts were rejected after stopping treatment. Next, we generated FGL2 transgenic mice (fgl2 Tg ) that ubiquitously overexpressed FGL2. These mice developed normally and had no evidence of the autoimmune glomerulonephritis seen in fgl2 À/À mice. Immune characterization showed fgl2Tg T cells were hypoproliferative to stimulation with alloantigens or anti-CD3 and anti-CD28 stimulation, and fgl2Tg Tregs had increased immunosuppressive activity compared with fgl2 +/+ Tregs. To determine if FGL2 overexpression can promote tolerance, we transplanted fully mismatched cardiac allografts into fgl2Tg recipients. Fifty percent of cardiac grafts were accepted indefinitely in fgl2Tg recipients without any immunosuppression. Tolerant fgl2Tg grafts had increased numbers and proportions of Tregs and tolerant fgl2Tg mice had reduced proliferation to donor but not third party antigens. These data show that tolerance in fgl2Tg recipients involves changes in Treg and T cell activity that contribute to a higher intragraft Treg-to-T cell ratio and acceptance of fully mismatched allografts.Abbreviations: BM, bone marrow; BMDC, bone marrow-derived dendritic cells; CAG, cytomegalovirus early enhancer/chicken b actin; CHO, Chinese hamster ovary; ConA, Concanavalin A; DC, dendritic cell; EGFP, enhanced green fluorescent protein; FGL2, fibrinogenlike protein 2; Foxp3, forkhead box P3; FReD, fibrinogen-related domain; IL, interleukin; MLR, mixed lymphocyte reaction; rFGL2, recombinant FGL2; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SMNC, splenic mononuclear cell; TIGIT, T cell immunoglobulin and ITIM domain; Treg, regulatory T cell

Autoantibodies directed against endogenous proteins including contractile proteins and endothelial antigens are frequently detected in patients with heart failure and after heart transplantation. There is evidence that these autoantibodies contribute to cardiac dysfunction and correlate with clinical outcomes. Currently, autoantibodies are detected in patient sera using individual ELISA assays (one for each antigen). Thus, screening for many individual autoantibodies is laborious and consumes a large amount of patient sample. To better capture the broad-scale antibody reactivities that occur in heart failure and post-transplant, we developed a custom antigen microarray technique that can simultaneously measure IgM and IgG reactivities against 64 unique antigens using just five microliters of patient serum. We first demonstrated that our antigen microarray technique displayed enhanced sensitivity to detect autoantibodies compared to the traditional ELISA method. We then piloted this technique using two sets of samples that were obtained at our institution. In the first retrospective study, we profiled pre-transplant sera from 24 heart failure patients who subsequently received heart transplants. We identified 8 antibody reactivities that were higher in patients who developed cellular rejection (2 or more episodes of grade 2R rejection in first year after transplant as defined by revised criteria from the International Society for Heart and Lung Transplantation) compared with those who did have not have rejection episodes. In a second retrospective study with 31 patients, we identified 7 IgM reactivities that were higher in heart transplant recipients who developed antibody-mediated rejection (AMR) compared with control recipients, and in time course studies, these reactivities appeared prior to overt graft dysfunction. In conclusion, we demonstrated that the autoantibody microarray technique outperforms traditional ELISAs as it uses less patient sample, has increased sensitivity, and can detect autoantibodies in a multiplex fashion. Furthermore, our results suggest that this autoantibody array technology may help to identify patients at risk of rejection following heart transplantation and identify heart transplant recipients with AMR.

Healthcare providers making preoperative clinical decisions for patients undergoing elective surgery should consider the degree of preoperative anemia and likelihood of perioperative transfusion.

Continuous-flow left ventricular assist devices (LVADs) are increasingly implanted to support patients with end-stage heart failure. These patients are at high risk for complications, many of which necessitate emergency care. While rehospitalization rates have been described, there is little data regarding emergency department (ED) visits. We hypothesize that ED visits are frequent and often require admission after LVAD implantation. We performed a retrospective review of patients in our health-care system followed by the advanced heart failure service for LVAD management after implantation between January 2011 and July 2015. We accounted for all ED visits in our system through February 2016, 7 months after the last implantation included. Clinically relevant demographic variables and ED visit details were recorded and analyzed to describe this population. We identified 81 patients with complete data, among whom there were 283 visits (3.49 visits/patient), occurring at a rate of approximately 7.3 ED visits per patient per year alive with LVAD. The most common reason for an ED visit is a complication related to bleeding (18% of visits), followed by chest pain (14%) and dizziness or syncope (13%). Thirty-six percent of patients were discharged from the ED without hospital admission. A growing populace with implanted LVADs represents an important population within emergency medicine. They are at risk for significant complications and frequently present to the ED. While many of these visits may be managed without hospital admission, this specialized patient group represents a potential area for improvement in provider education.

SummaryHigh-frequency oscillatory ventilation (HFOV) can improve ventilation-perfusion matching without excessive alveolar tidal stretching or collapse-reopening phenomenon. This is an attractive feature in the ventilation of patients with ARDS. However, two recent large multi-center trials of HFOV failed to show benefits in this patient population. The following review addresses whether, in view of these trails, HFOV should be abandoned in the adult population? Key words: acute respiratory failure; high-frequency oscillatory ventilation. [Respir Care 2016;61(6):791-800.