AbstractProfessor Stephen J. Galli's rigorous and innovative research in the field of allergy and immunology has truly made him a legend in the field. His accomplishments are many as are the awards and recognitions he has received. He and his team have published approximately 430 peer‐reviewed publications and 14 patents. He has chaired, organized, or co‐organized 16 scientific meetings or symposia. Some of the major awards he has received are the MERIT award from NIAID/NIH (1995), Scientific...
Tue Apr 09, 2019 18:08
AbstractImbalance, or dysbiosis, of the gut microbiome of infants has been linked to an increased risk of asthma and allergic diseases. Most studies to date have provided a wealth of data showing correlations between early‐life risk factors for disease and changes in the structure of the gut microbiome that disrupt normal immunoregulation. These studies have typically focused on one specific risk factor, such as mode of delivery or early‐life antibiotic use. Such 'micro‐level' exposures have...
Tue Apr 09, 2019 11:04
AbstractBackgroundEpicutaneous sensitization is an important route of immunization for allergens in atopic diseases; however, studies have also shown that application with protein on intact skin induces antigen‐specific tolerance. Langerhans cells (LCs) play an immunosuppressive role in several inflammatory skin diseases and mouse models, and the role of LCs in the skin‐induced tolerance is not fully understood.MethodsLangerin‐DTA mice that were deficient in LCs were utilized to produce the...
Tue Apr 09, 2019 11:04
AbstractPerioperative immediate hypersensitivity reactions are rare. Subsequent allergy investigation is complicated by multiple simultaneous drug exposures, the use of drugs with potent effects and the many differential diagnoses to hypersensitivity in the perioperative setting. The approach to the investigation of these complex reactions is not standardized and it is becoming increasingly apparent that collaboration between experts in the field of allergy/immunology/dermatology and anaesthesiology...
Tue Apr 09, 2019 18:07
AbstractThe term allergy was coined in 1906 by the Austrian scientist and paediatrician Clemens Freiherr von Pirquet, head of the Department of Paediatrics in Vienna from 1912 to 1929. His successor, Franz Hamburger, obliterated all references to Pirquet, especially the term allergy, creating a large gap in allergy research until the 1960s. The University of Vienna Dermatology and ENT departments performed skin prick tests and hyposensitizations well into the late 1970s, but no basic scientific...
Tue Apr 09, 2019 18:06
AbstractPeriostin is a matricellular protein as well as an extracellular matrix (ECM) protein belonging to the fasciclin family. Periostin plays important roles as a matricellular protein in the setting of allergic diseases by binding to several integrins on various cells. Since periostin is induced mainly by IL‐4 and IL‐13, signature type 2 cytokines, and it is highly expressed in the subepithelial regions of many chronic allergic diseases, periostin has emerged as a novel biomarker reflecting...
Tue Apr 09, 2019 18:02
AbstractAllergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence‐based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including health professionals. The decision to prescribe AIT for the patient should...
Sun Apr 07, 2019 13:48
BackgroundEndoscopic skull‐base surgery (ESBS) is a rapidly growing discipline that often combines the expertise of otolaryngology–head and neck surgeons and neurosurgeons to provide care for these challenging conditions. As the field has grown, so too has the literature evaluating this surgical approach and the challenges and complications associated with these interventions. An international, multidisciplinary effort to critically evaluate and grade the current literature on ESBS has resulted...
Mon Apr 08, 2019 12:08
We read with great interest the article titled "Allergen-induced activation of natural killer cells represents an early life immune response in development of allergic asthma" by Altman et al.1 The study revealed a novel mechanistic insight into the development of allergic asthma. However, some technical issues need to be clarified.
Tue Apr 09, 2019 03:00
We appreciate the interest from Lu et al1 regarding our article titled "Allergen-induced activation of natural killer cells represents an early-life immune response in the development of allergic asthma."2 The readers' first question asks about the cellular source of the gene expression signature that we identified in this article. This is a very important question and limitation of our study, and one that we consider in the article discussion. However, the readers specifically question whether myeloid-derived...
Tue Apr 09, 2019 03:00
This study reveals that TH2 and TH17 cytokines can regulate epithelium-derived CST1 expression. CST1 activates eosinophils and promotes their infiltration via IL-5-mediated pathway. CST1 represents a new promising target for the treatment of ECRSwNP.
Mon Apr 08, 2019 03:00
Mon Apr 08, 2019 23:00
Inflammasomes are protein complexes that respond to a wide range of pathogens and cellular damage signals. Their activation prompts the caspase-1–mediated cleavage of the proinflammatory cytokines IL-1β and IL-18. Inflammasome dysregulation has been demonstrated to play a role in a range of diseases involving the adaptive immune system like multiple sclerosis, rheumatic diseases, and type 1 diabetes. Priming and activation of inflammasomes can be modulated by microRNAs (miRNAs), small noncoding RNAs...
Mon Apr 08, 2019 23:00
OmpU, one of the porins of Gram-negative bacteria Vibrio cholerae, induces TLR1/2–MyD88–NF-B–dependent proinflammatory cytokine production by monocytes and macrophages of human and mouse origin. In this study, we report that in both the cell types, OmpU-induced proinflammatory responses involve activation of MAPKs (p38 and JNK). Interestingly, we observed that in OmpU-treated macrophages, p38 activation is TLR2 dependent, but JNK activation happens through a separate pathway involving reactive oxygen...
Mon Apr 08, 2019 23:00
Neutrophils are essential during contact hypersensitivity (CHS), a common skin allergic disease. NF-E2–related factor-2 (Nrf2) is a key regulator of redox balance and skin homeostasis playing a protective role in CHS. In this study, we investigated Nrf2 role in neutrophil recruitment during the sensitization phase of CHS. Comparing wild-type and Nrf2 knockout mice, we demonstrated that Nrf2 regulated dinitrochlorobenzene-induced xenoinflammation, notably neutrophil recruitment to sensitized skin....
Mon Apr 08, 2019 23:00
MyD88 adaptor-like (Mal) protein is the most polymorphic of the four key adaptor proteins involved in TLR signaling. TLRs play a critical role in the recognition and immune response to pathogens through activation of the prototypic inflammatory transcription factor NF-B. The study of single nucleotide polymorphisms in TLRs, adaptors, and signaling mediators has provided key insights into the function of the corresponding genes but also into the susceptibility to infectious diseases in humans. In...
Mon Apr 08, 2019 23:00
Regulatory T cell (Treg) therapy is a potential curative approach for a variety of immune-mediated conditions, including autoimmunity and transplantation, in which there is pathological tissue damage. In mice, IL-33R (ST2)–expressing Tregs mediate tissue repair by producing the growth factor amphiregulin, but whether similar tissue-reparative Tregs exist in humans remains unclear. We show that human Tregs in blood and multiple tissue types produced amphiregulin, but this was neither a unique feature...
Mon Apr 08, 2019 23:00
The TNFR superfamily member 4-1BB is important in the establishment of tissue-resident memory T cells (Trm) in the lung tissue following influenza infection. Moreover, supraphysiological boosting of 4-1BB in the airways during the boost phase of a prime-boost immunization regimen increases the long-lived Trm population, correlating with increased protection against heterotypic challenge. However, little is known about how 4-1BB contributes to the establishment of the lung Trm population. In this...
Mon Apr 08, 2019 23:00
The aim of this study was to test whether autoantibodies against neurologic surface Ags are found in nonneurologic autoimmune diseases, indicating a broader loss of tolerance. Patient and matched healthy donor (HD) sera were derived from four large cohorts: 1) rheumatoid arthritis (RA) (n = 194, HD n = 64), 2) type 1 diabetes (T1D) (n = 200, HD n = 200), 3) systemic lupus erythematosus (SLE) (n = 200, HD n = 67; neuro-SLE n = 49, HD n = 33), and 4) a control cohort of neurologic autoimmunity (relapsing-remitting...
Mon Apr 08, 2019 23:00
Mast cells (MCs) contribute to the control of local inflammatory reactions and become hyporesponsive after prolonged TLR4 activation by bacterial LPS. The molecular mechanisms involved in endotoxin tolerance (ET) induction in MCs are not fully understood. In this study, we demonstrate that the endocannabinoid 2-arachidonoylglycerol (2-AG) and its receptor, cannabinoid receptor 2 (CB2), play a role in the establishment of ET in bone marrow–derived MCs from C57BL/6J mice. We found that CB2 antagonism...
Mon Apr 08, 2019 23:00
Key PointsThe Ab repertoire is diversified through the acquisition of N-glycosylation sites. Frequencies of V region N-glycosylation sites are isotype and subclass dependent. Elevated Fab glycosylation is an additional hallmark of TH2-like IgG4/IgE responses.
Mon Apr 08, 2019 23:00
Key PointsFTRCA1 is a crucian carp–specific member of finTRIM. FTRCA1 downregulates fish IFN response through lysosomal degradation of TBK1. The E3 ligase activity is likely required for FTRCA1 function on TBK1 degradation.
Mon Apr 08, 2019 23:00
T follicular helper (Tfh) cells are a specialized T cell subset that regulates the long-lived production of highly specific Abs by B cells during the germinal center (GC) reaction. However, the transcriptional network sustaining the Tfh cell phenotype and function is still incompletely understood. In this study, we identify the transcription factor Bach2 as a central negative regulator of Tfh cells. Ectopic overexpression of Bach2 in murine Tfh cells resulted in a rapid loss of their phenotype and...
Mon Apr 08, 2019 23:00
KEY POINTSNotch favors RUNX1 and MYB recruitment to activate enhancer-dependent transcription. These results decipher the mechanism for Tcrd and Tcrg silencing during β-selection.
Mon Apr 08, 2019 23:00
Alpha-1 antitrypsin (AAT) is an acute phase protein that possesses immune-regulatory and anti-inflammatory functions independent of antiprotease activity. AAT deficiency (AATD) is associated with early-onset emphysema and chronic obstructive pulmonary disease. Of interest are the AATD nonsense mutations (termed null or Q0), the majority of which arise from premature termination codons in the mRNA coding region. We have recently demonstrated that plasma from an AATD patient homozygous for the Null...
Mon Apr 08, 2019 23:00
IFN- is a key cytokine of innate and adaptive immunity. It is important to understand temporal changes in IFN- production and how these changes relate to the role of IFN- in diverse models of infectious and autoimmune disease, making the ability to monitor and track IFN- production in vivo of a substantial benefit. IFN- ELISPOTs have been a central methodology to measure T cell immunity for many years. In this study, we add the capacity to analyze IFN- responses with high sensitivity and specificity,...
Mon Apr 08, 2019 23:00
Key PointsIRF3 is phosphorylated by Abl kinase family. c-Abl and Arg regulate innate immunity by promoting type I IFN production. AIM2 inflammasome activation during Ft LVS infection is prompted by Abl kinase.
Mon Apr 08, 2019 23:00
Key PointsIFN-β promotes host resistance to M. tuberculosis via induction of NO production. Capacity to inhibit IFN-β signaling correlates with mycobacterial virulence. M. tuberculosis limits activation of receptor-associated tyrosine kinases TYK2 and JAK1.
Mon Apr 08, 2019 23:00
It is not clear how hepatitis B virus (HBV) modulates host immunity during chronic infection. In addition to the key mediators of inflammatory response in viral infection, monocytes also express a high-level IFN-stimulated gene, CH25H, upon response to IFN-α exerting an antiviral effect. In this study, the mechanism by which HBV manipulates IFN signaling in human monocytes was investigated. We observed that monocytes from chronic hepatitis B patients express lower levels of IFN signaling/stimulated...
Mon Apr 08, 2019 23:00
Decreased inflammation and cardiovascular mortality are evident in patients with end-stage chronic kidney disease treated by online hemodiafiltration. Extracellular vesicles (EV) are mediators of cell-to-cell communication and contain different RNA types. This study investigated whether mixed online hemodiafiltration (mOL-HDF) beneficial effects associate with changes in the RNA content of plasma EV in chronic kidney disease patients. Thirty bicarbonate hemodialysis (BHD) patients were randomized...
Mon Apr 08, 2019 23:00
Key PointsShp1-deficient iNKT cells are biased toward the iNKT2/17 subsets. Shp1 deficiency does not alter TCR or Slam signaling. Shp1 dampens iNKT cell proliferation in response to cytokines.
Mon Apr 08, 2019 23:00
Key PointsKnockout of USP20 inhibits HSV-1– but not Sendai virus–triggered signaling. USP20-deficient mice exhibit increased susceptibility to HSV-1 infection. USP20 deconjugates K48-linked polyubiquitin chains from and thereby stabilizes MITA.
Mon Apr 08, 2019 23:00
Key PointsNKAP Y352 is required for association with HDAC3. The interaction between NKAP and HDAC3 is critical for its function in HSCs. The interaction between NKAP and HDAC3 is unimportant in some cell types.
Mon Apr 08, 2019 23:00
TLR-induced signaling potently activates cells of the innate immune system and is subject to regulation at different levels. Inflammatory conditions are associated with increased levels of extracellular adenosine, which can modulate TLR-induced production of cytokines through adenosine receptor–mediated signaling. There are four adenosine receptor subtypes that induce different signaling cascades. In this study, we demonstrate a pivotal contribution of adenosine A3 receptor (A3R)–mediated signaling...
Mon Apr 08, 2019 23:00
Key PointsSostdc1 influences tNK to mNK cell differentiation and the Ly49 receptor repertoire. NK cells in Sostdc1–/– mice display impaired ability to kill β2m–/– target cells. Sostdc1 expression in stromal and hematopoietic cells regulates NK cells.
Mon Apr 08, 2019 23:00
Key PointsLoss of adipocyte and macrophage H2Ab1 leads to no change in metabolic phenotype. Specific loss of macrophage H2Ab1 leads to improvements in glucose tolerance. Adipocytes on HFD express LysM and are targeted by the LysMCre model.
Mon Apr 08, 2019 23:00
Key PointsWe engineered the Fc of human IgG to increase its affinity for TRIM21 by 100-fold. The engineered Fc enhances cross-presentation in monocyte-derived dendritic cells. Our finding may be applied to vaccine design to boost CD8 T cell–based immunity.
Mon Apr 08, 2019 23:00
Helminthic infections modulate host immunity and may protect their hosts from developing immunological diseases like inflammatory bowel disease. Induction of regulatory T cells (Tregs) may be an important part of this protective process. Heligmosomoides polygyrus bakeri infection also promotes the production of the regulatory cytokines TGF-β and IL-10 in the gut. In the intestines, TGF-β helps induce regulatory T cells. This study used Foxp3/IL-10 double reporter mice to investigate the effect of...
Mon Apr 08, 2019 23:00
Adenoviral vectors can induce T and B cell immune responses to Ags encoded in the recombinant vector. The MHC class II invariant chain (Ii) has been used as an adjuvant to enhance T cell responses to tethered Ag encoded in adenoviral vectors. In this study, we modified the Ii adjuvant by insertion of a furin recognition site (Ii-fur) to obtain a secreted version of the Ii. To test the capacity of this adjuvant to enhance immune responses, we recombined vectors to encode Plasmodium falciparum virulence...
Mon Apr 08, 2019 23:00
The limited number of hematopoietic stem cells (HSC) within a single unit of human cord blood currently limits its use as an alternate graft source. However, we have developed a strategy using 5-aza-2'-deoxycytidine (5azaD) and trichostatin A (TSA), which expands transplantable HSC 7- to 10-fold. In our current studies, we have assessed the allostimulatory capacity of the 5azaD/TSA-expanded grafts. The coexpression of immunophenotypic dendritic cell (DC) markers, such as HLA-DR/CD86 and HLA-DR/CD11c...
Mon Apr 08, 2019 23:00
Epithelial barrier cells are proposed to be critical for host defense, and airway epithelial cell capacity for IFN signal transduction is presumed to protect against respiratory viral infection. However, it has been difficult to fully test these concepts given the absence of tools to analyze IFN signaling specific to airway epithelial cells in vivo. To address these issues, we generated a new line of transgenic mice with Cre-driver genes (Foxj1 and Scgb1a1) for a floxed-Stat1 allele (designated Foxj1-Scgb1a1-Cre-Stat1f/f...
Mon Apr 08, 2019 23:00
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