bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a novel subset of activation induced deaminase (AID)-dependent B-1 cells that mediate Initiation of Contact Sensitivity (37.10)
Authors: Kerfoot Steven M , Szczepanik Marian , Tung James , Herzenberg Leonore A , Askenase Philip W 
Published: January 2023

Abstract
Contact sensitivity (CS) to haptens is related to delayed type hypersensitivity (DTH) and is a well characterized prototype of T cell mediated inflammation. CS is additionally dependent on a parallel immune pathway. In response to sensitization, a population of B-1 cells produces antigen-specific IgM which mediates a rapid inflammatory response to hapten re-exposure. Interference with this pathway prevents the full development of the classic delayed response and is therefore termed the “CS-Initiation” pathway. The identity of the B-1 cell subset responsible for CS-Initiation is not known. Here, we show that CS-Initiation is dependent on activation induced deaminase (AID), an enzyme central to the process of somatic hypermutation (SHM). Using adoptive transfer experiments, we demonstrate that the defect is specific to B-1 cells as transfer of wild type B-1 cells reconstitutes CS-Initiation in deficient recipients. We went on to identify and characterize a unique subpopulation of B-1 cells in the spleens of sensitized mice that possess initiation activity. Detailed analysis of B cell receptor genes isolated from these cells revealed evidence of AID-mediated SHM. The sensitivity of CS-Initiation to very low amounts of hapten and the dependence on AID suggests that these cells are selected to generate antibodies capable of mediating CS-Initiation.
This work funded by the Canadian Institutes of Health Research, the American Academy of Allergy, Asthma and Immunology and the National Institutes of Health.
Effect of staphylococcal enterotoxin B antigen on atopic dermatitis-like lesion induced by contact allergen in hairless mice (37.13)
Authors: Lee Jong Kwon , Ju Jung Hun , Kim Jinho , Kim Jung Rae , Chun Eun Young , Kim In Young , Sohn Kyung Hee , Kim Seung Hee , Park Kui Lea 
Published: January 2023

Abstract
Atopic dermatitis (AD) is a common pruritic disease and its incidence is increasing in infancy and childhood. Patients with AD have reported cutaneous to both environmental and superantigen-producing strains of Staphylococcal aureus. In this study, we investigated the effect of staphyloccoal enterotoxin B (SEB) antigen on atopic dermatitis-like lesion induced by dinitrochlorobenzene (DNCB) in hairless mice. We treated the DNCB or DNCB+SEB topically on the skin of hairless mice. Repeated epicutaneous sensitization with DNCB or DNCB+SEB induced AD-like skin lesions including erythema followed edema, excoriation and scaling. The histologic features of the skin site in mice treated with DNCB or DNCB+SEB showed epidermal hyperplasia with hyperkeratosis, severe infiltration of eosinophils and increase of mast cells in dermis. The DNCB+SEB-sensitized skin site showed slightly increase in infiltration of eosinophils in dermis compared with DNCB-sensitized skin sites. The serum level of IgE in DNCB+SEB group showed slightly increase compared to the DNCB group. The serum level of IgG2a in DNCB+SEB group showed significantly increase compared to the DNCB. The serum level of IgG1 and IgG2b in DNCB+SEB group showed slightly increase compared to the DNCB. These results suggest that topical exposure to SEB slightly provokes AD-like lesion and hypersensitivity response induced by DNCB in mice.
Shift from IL-3- to IgE-induced IL-4 production as basophils become a predominant source of IL-4 (37.15)
Authors: Yang Junqi , Khodoun Marat , Orekov Tatyana , Mohrs Katja , Potter Crystal , Mohrs Markus , Finkelman Fred D. 
Published: January 2023

Abstract
We compared CD4+ T cell and basophil contributions to in vivo IL-4 production and evaluated stimuli that induce basophil IL-4 production during immune responses to a protein Ag, goat anti-mouse IgD antiserum (GaMD), and a nematode parasite. IL-4 production by basophils preceded CD4+ T cells, but CD4+ T cells produced most IL-4 secreted during the primary response to GAMD and the secondary response to Ag challenge 4–5 d after priming. In contrast, basophils produced most of the IL-4 secreted in mice challenged 12–14 d after priming. Basophil IL-4 secretion was IL-3-dependent but influenced by IgE during the primary response and IL-3- and CD4+ T cell-dependent/IgE-independent during the d 4–5 secondary response, but was IgE-dependent and IL-3/CD4+ T cell-independent during the d 12–14 secondary response. Basophil IL-4 secretion during a primary infection with Trichinella spiralis was localized to the liver and was partially IL-3- and IgE-independent. Thus, IL-3-dependent basophil IL-4 production precedes and supplements the primary T cell IL-4 response to a protein Ag; basophil IL-4 production can exceed T cell IL-4 production in animals challenged with Ag after basophils are primed by Ag-specific IgE; and helminthic parasites can stimulate basophil IL-4 secretion through a distinct mechanism.
CD8+ Tc1 and TIL-17 cells mediate allergic contact hypersensitivity by different mechanisms (37.18)
Authors: He Donggou , Wu Lizhi , Kim Hee Kyung , Li Hui , Elmets Craig A , Xu Hui 
Published: January 2023

Abstract
Allergen induced contact hypersensitivity(CHS) in the skin has been considered to be mediated by CD4+ Th1 and CD8+ Tc1 cells that produce IFN-γ. Our recent studies have demonstrated that CD8+ IL-17 producing T cells (TIL-17) play important roles in the elicitation of CHS. Allergen sensitization induces the development of CD8+ Tc1 and TIL-17 cells that are distinct T cell subpopulations. Here we demonstrate that both CD8+ Tc1 and TIL-17 cells play a role in the elicitation of CHS. However, they mediate inflammatory reactions in the skin by different mechanisms. CHS was reduced but not abolished in mice that were defect in the receptor for IFN-γ (IFN-γR−/−) or IL-17 (IL-17R−/−) compared to wild type controls. Similar results were observed in the adoptive transfer of CHS in the gene knockout mice that were transferred with allergen primed wild type CD8+ T cells. However, neutralization of IL-17 in IFN-γR−/− or IFN-γ in IL-17R−/− recipient mice abrogated the response. It implicates that both IFN-γ and IL-17 signals are involved in the elicitation of CHS and are required for optimal responses. Immunohistochemical analysis indicated that the infiltration of Gr-1+ granulocytes and CD11b+ macrophages in the allergen challenged skin of IL-17R−/− mice was significantly reduced whereas it was slightly affected in IFN-γR−/− mice. Further analysis using real time RT-PCR showed different patterns of chemokines and inflammatory cytokines in the allergen challenged skin of IFN-γR−/− or IL-17R−/− mice. These data indicate that both CD8+ Tc1 and TIL-17 cells take part in the elicitation of CHS and that specific mechanisms orchestrate Tc1 and TIL-17 mediated inflammatory reactions in the skin. The result of current studies may provide new insights into therapeutic strategies for T cell mediated inflammatory disorders.
THE ACETYLCHOLINESTERASE INHIBITOR MALATION IS NOT TOXIC TO THYMOCYTES, BUT MAY ALTER THE DEVELOPMENTAL PROGRAM AT LOW DOSES. (37.2)
Authors: Broussard Christine , Varney Jessica 
Published: January 2023

Abstract
The incidence of allergy and asthma among children has risen 150% in the last two decades in children under five years old, and environmental pollutants are suspected to be contributors to this rise in incidence. Environmental pollutants, such as pesticides, are known to have a negative impact on the environment as well as many living organisms. However, there are a limited number of studies that have investigated the impact pesticides have on the immune system of mammals. Futhermore, even fewer studies exist that examine the impact of environmental toxicants on the immune system of the developing embryo and young animal, though the immune systems of the young are more vulnerable to perturbation than that of adults. Therefore risk assessment studies addressing fetal immune development are important tools for better understanding whether pesticides and other environmental toxicants contribute to immune system diseases that are widely common today. We set up an in vitro model system to assess the risk of exposure to the pesticide Malathion. Malathion was chosen for the study because of its widespread use in agriculture and the known role it plays as an acetylcholinesterase inhibitor. We analyzed the response of day 16–18 embryonic thymocytes to varying concentrations of Malathion. We hypothesized that greater concentrations of the pesticide would have a greater toxicity in T cells. Flow cytometric analysis was used to determine the level of toxicity and maturation of the embryonic T cells following culture.
J.V. is a ULV undergraduate researcher.
Rgs13 inhibits IgE-mediated allergic responses (37.5)
Authors: Bansal Geetanjali , Xie Zhihui , Druey Kirk 
Published: January 2023

Abstract
Mast cells (MCs) evoke immediate hypersensitivity by degranulating in response to antigen (Ag) exposure and releasing preformed mediators such as histamine and leukotreines. Classically, the high affinity immune receptor for immunoglobulin E (FcεRI) mediates MC degranulation and anaphylaxis in response to antigen. In addition, various G protein coupled receptors (GPCRs) on MCs such as those for adenosine and sphingosine-1-phosphate (S1P) may also activate MCs. Since GPCR signaling is inhibited by Regulator of G protein Signaling (RGS) proteins, we studied the potential regulation of MC activation by RGS proteins. We identified Rgs1, 8, 13 and 18 in murine bone marrow-derived MCs (BMMCs). Rgs13−/− (KO) mice with LacZ knock-in were generated. Surprisingly, G protein-mediated degranulation induced by either adenosine or S1P was similar in WT and KO mice. In contrast, IgE/Ag -dependent degranulation and intracellular Ca++ flux as well as in vivo passive cutaneous anaphylaxis responses were significantly higher in KO BMMCs suggesting that Rgs13 affects IgE/Ag dependent pathway rather that GPCR-mediated pathway leading to MC activation. Reconstitution of KO BMMCs with WT Rgs13 inhibited degranulation to IgE/Ag. Analysis of effectors downstream of FcεRI revealed that Rgs13 interacts with PI3K and inhibits its activation in response to IgE/Ag. Thus, Rgs13 could represent a new therapeutic target for MC-dependent allergic responses.
Work was funded by DIR, NIAID/NIH.
The role of Rab27A in human eosinophil exocytosis (38.3)
Authors: Coughlin Jason J , Moqbel Redwan 
Published: January 2023

Abstract
Eosinophils play an effector role in airway damage in asthma and related disorders, since their secreted granule-stored products can induce many of the clinical features of asthma. Degranulation of eosinophils requires the activity of several GTP-binding proteins, many of which remain unidentified. We hypothesized that Rab27A is one of these GTP-binding proteins because, in other cells, it interacts with effectors that regulate vesicle motility, docking and fusion. Humans with Rab27A-deficiency develop Griscelli syndrome which is characterized by immunodeficiency and partial albinism due to secretory defects in various cell types. We have established that Rab27A is expressed in human peripheral blood eosinophils as determined by RT-PCR and Western blotting. To asses Rab27A activation we developed a novel assay allowing the pulldown of the active, GTP-bound form. Rab27A was activated in several leukocyte populations upon cell stimulation with degranulatory stimuli. In human eosinophils, Rab27A was transiently activated by secretory-IgA stimulation. Rab27A activation followed a temporal pattern similar to that of degranulation, suggesting that Rab27A activation induces secretory granule movement and exocytosis. A clearer understanding of granulocyte exocytosis may contribute to novel therapeutic strategies in asthma, allergic inflammation and related conditions.
Funding provided by the Canadian Institutes of Health Research and the Alberta Heritage Foundation for Medical Research
Skewed polarization of pulmonary dendritic cells in RSV-infection and susceptibility to asthma (39.2)
Authors: Qureshi Mahboob Hossain , Durre Kainathk , Yang William 
Published: January 2023

Abstract
Respiratory syncytial virus (RSV) infection accounts for significant morbidity in young infants. The survivors become susceptible to develop asthma later in life. Studies have shown increased airway responsiveness in these individuals and a concomitant Th2 response in their lungs. However, the underlying mechanism (s) responsible for this pulmonary Th2 response in post- RSV infection period is not well understood. In this study, using a mouse model, we examined whether differentiation of lung dendritic cells (DCs) was skewed due to RSV infection and whether a Th2 cytokine response was associated. Neonatal mice were sensitized with intraperitoneal ovalabumin (ova) and infected with intranasal RSV followed by subsequent challenge with intranasal ova. Flowcytometric analysis of lung parenchymal cells determined the proportions of CD11bloCD11chiCD45R- myeloid DCs (mDCs) and CD11blo CD11chi CD45Rhi plasmacytoid DCs (pDCs). An increase in the numbers of pDCs was observed in the lungs of RSV-infected as well as RSV-infected and ova-exposed mice. To mention, pDCs are reported to downregulate Th1 responses. Consistent to this, augmentation of Th2 cytokine responses was observed in the RSV-infected and ova-exposed mice. Thus, polarization of lung DCs towards pDC due to RSV infection may modulate lung cytokine responses leading to susceptibility to asthma in later life. Reversal or inhibition of this skewed polarization may be considered as a clinical strategy in the post-RSV infection asthma. In this connection, we have reported that GMCSF and IL4 treatment expands lung dendritic cell population with enhanced Th1 responses.
Effects of Lactose-b-sitosterol And b-sitosterol On Ovalbumin–induced Asthmatic Mice (39.3)
Authors: Kim In Sik , Yuk Ji Eun , Yun Chi-Young , Lee Ji-Sook , Kim Dong-Hee , Kim Joo-Whan , Yang Eun Ju 
Published: January 2023

Abstract
Asthma is a chronic lung inflammation and patients suffering from it annually increases. Both β-sitosterol (BS) and β-sitosterol glucoside exist in a variety of plants. However, the precise role of BS and β-sitosterol glucoside in asthma has not been understood well. The aim of this study was to investigate the inhibitory effects of BS and lactose-BS (L-BS) on the pathophysiological process in asthma. For this purpose, BALB/c mice were immunized through i.p. injection with OVA and aluminum hydroxide on days 1 and 14. From days 21 to 27, the mice were exposed to 5% ovalbumin solution aerosolized for 1 hr per day. Total cells and eosinophils in BAL fluid markedly decreased after L-BS or BS treatment (p &lt; 0.05) and ROS production also lessened as compared to asthma control. Both L-BS and BS strongly mitigated mucus hypersecretion by goblet hyperplasia and inflammation by eosinophil infiltration. These effects of L-BS were superior to those of BS. Both L-BS and BS inhibited the mRNA and protein expression of IL-4 and IL-5 in the lung tissue and BALF, respectively. Ovalbumin-specific IgE in BALF was uniquely inhibited by L-BS (p &lt; 0.05). This finding provides the possibility of L-BS and BS as therapeutic drugs in asthma and it may contribute the need to improve current therapeutic drugs.
Acknowledgment This work was supported by RIC(R) grants from Traditional and BioMedical Research Center, Daejeon University (RRC04730, 2005) by ITEP.
Follistatin is a candidate endogenous negative regulator of activin A in experimental allergic asthma (39.7)
Authors: Hardy Charles Linton , Nguyen Hong-An , Yao Jun , De Kretser David M , Rolland Jennifer M , Anderson Gary P , Phillips David J , O’Hehir Robyn E 
Published: January 2023

Abstract
Background: Activin A is a member of the TGF-β superfamily implicated in asthmatic inflammation and tissue remodelling. In vitro, activin A bioactivity is neutralized by the soluble binding protein follistatin.
Objective: To determine the potential of endogenous follistatin to suppress activin A in vivo by analysing their relative tissue and kinetic compartmentalization in acute and chronic allergic airway inflammation.
Methods: Ovalbumin-sensitized mice were subjected to acute or chronic allergen challenge protocols. Kinetics and distribution of activin A and follistatin were measured in lung tissue and BAL in relation to airway eosinophilia, Th2 cytokines, mucus production and collagen deposition.
Results: In both models peak BAL activin A and follistatin concentrations coincided with maximal airway eosinophilia, and frequency of IL-4, IL-5 and IL-13 producing cells in draining lymph nodes; follistatin and activin A immunoreactivity were lost in airway epithelium in parallel with goblet cell metaplasia. In the chronic model inflammation preceded remodelling associated with elevated BAL activin A and TGF-β. Exogenous follistatin inhibited acute allergic airway inflammation.
Conclusion: Follistatin is preformed in the normal lung and released in concert with activin A suggesting it serves as an endogenous regulator. Follistatin has potential as a therapeutic to limit airway remodelling.
Differential accumulation of IgA ASC in sublingual vs. submaxillary salivary glands is directly correlated with the level of CCL28 expression. (40.4)
Authors: Law Yuetching , Hill Erica D , Distelhorst Kathryn , Wilson Eric 
Published: January 2023

Abstract
Optimal function of the immune system is highly dependent on efficient homing and accumulation of leukocytes. The homing of leukocytes has been shown to be dependent on interactions between leukocyte expressed chemokine receptors and adhesion molecules, and tissue expressed chemokines and adhesion molecule ligands. The homing and accumulation of IgA antibody secreting B cells (ASC) to mucosal tissues is thought to be highly dependent upon leukocyte expressed chemokine receptors CCR9 and CCR10 interacting with the chemokines CCL25 and CCL28 respectively. CCL28 has been shown to be involved in the homing of IgA ASC to the gastrointestinal tract and the lactating mammary gland, but has not been demonstrated to play a role, in vivo, in the accumulation of IgA ASC to other mucosal tissues. CCL28 has been shown to be expressed in mouse salivary glands. Here we show that CCL28 is expressed at higher levels in mouse sublingual salivary glands than in submaxillary salivary glands. This higher level of expression in the sublingual gland correlates directly with greater numbers of IgA ASC in the sublingual gland compared with the submaxillary gland. These results demonstrate differential accumulation of IgA ASC into mouse salivary glands and suggest that this difference in lymphocyte accumulation is at least in part the result of differential expression of CCL28.
MyD88-dependent regulation of the polymeric immunoglobulin receptor by colonic microbes (40.5)
Authors: Stefka Andrew T , Bruno Maria EC , Kaetzel Charlotte S 
Published: January 2023

Abstract
Secretory IgA serves as the first line of antigen-specific immunity in the intestine, protecting against pathogens while preventing inflammation in response to commensal microbes. Intestinal epithelial cells (IEC) regulate IgA secretion by controlling expression of the polymeric immunoglobulin receptor (pIgR). Many pro- and anti-inflammatory factors, including pIgR, are transcriptional targets of Toll-like receptor (TLR) signaling in response to molecular patterns from resident microbes. MyD88 is an important TLR signaling adaptor that has been implicated in regulation of intestinal inflammation. To assess the role of MyD88 in IEC gene expression, we compared mRNA levels of pIgR, TNF, and two regulatory factors, A20 and MKP-1, in the small intestines and colons of wild-type and MyD88−/− mice. Gene expression was significantly higher in the colon than in the small intestine of all mice, correlating with the higher microbial load. In the colon, expression of all genes was significantly higher in wild-type than in MyD88−/−mice. We conclude that commensal microorganisms set the tone of intestinal gene expression through MyD88-dependent TLR signaling.
Supported by Crohn’s & Colitis Foundation of America.
Beta7-integrin independent enhancement of mucosal and systemic anti-HIV antibody responses following combined mucosal and systemic gene delivery (41.1)
Authors: Vajdy Michael , Goodsell Amanda , Zhou Fengmin , Singh Manmohan , Malyala Padma , Kazzaz Jina , Greer Catherine , Megede Jan zur , Barnett Susan , O’Hagan Derek , Polo John 
Published: January 2023

Abstract
Vaccination strategies that can block or limit heterosexual HIV transmissions to local and systemic tissues are much sought for. Herein, in a mouse model, we aimed to determine whether the enhancement of antibody responses through mucosal and systemic immunizations, previously observed with protein-based vaccines, applies to immunizations with DNA- or RNA-based vectors. Intra-nasal (i.n.) followed by intra-muscular (i.m.) immunizations (i.n./i.m.) with PLG-DNA microparticles encoding HIV-gag (PLG-DNA-gag) significantly enhanced serum antibody responses, compared i.m., i.n. or i.m. followed by i.n. (i.m./i.n.), immunizations. Moreover, while i.n./i.m., i.n. or i.m./i.n. immunizations with PLG-DNA-gag resulted in genital tract antibody responses, i.m. immunizations alone failed to do so. Importantly, β7-deficient mice developed local and systemic antibody responses following i.n./i.m., or any other routes of immunization similar to wild type mice. To compare the DNA with an RNA delivery system, immunizations were performed with VEE/SIN-gag replicon particles, composed of Venezuelan Equine Encephalitis virus (VEE) replicon RNA and Sindbis surface structure (SIN). i.n./i.m., as compared to any other immunizations, with VEE/SIN-gag resulted in enhanced genital tract, but not serum antibody responses. These data show for the first time that mucosal followed by systemic immunizations with gene delivery systems enhance B cell responses independent of the mucosal homing receptors α4β7 or αEβ7.
Expression and subcellular targeting of a model subunit vaccine in transgenic soybean (41.13)
Authors: Oakes Judy Lynn , Garg Renu , Bost Kenneth L. , Piller Kenneth J. 
Published: January 2023

Abstract
Enterotoxigenic Escherichia coli (ETEC) strains are the leading cause of enteric diseases affecting humans and livestock. Edible transgenic plants producing E. coli fimbrial subunit proteins have the potential to vaccinate against these diseases by delivering naturally encapsulated antigens to effecter sites lining the gastrointestinal tract and eliciting mucosal as well as systemic immunity. Plants, however, have not reached their full potential as a renewable source of oral vaccines, due in part to insufficient levels of recombinant protein accumulation. In an effort to increase the relative amount of subunit vaccine candidate in a practical host system, we targeted the agricultural antigen, FanC, to soybean chloroplasts. We monitored FanC mRNA expression and protein production, demonstrated proper chloroplast accumulation of the protein, and compared the amounts of this chloroplast targeted-protein to accumulation of cytosol-targeted FanC. Surprisingly, cytosol-targeted FanC accumulation was 5-fold greater than chloroplast-targeted FanC accumulation, despite similar FanC mRNA transcription levels in cytosol and chloroplast targeted events. Intraperitoneal vaccination of mice with the chloroplast-derived antigen induced an anti-FanC IgG immune response similar to that generated by vaccination with cytosol-derived and recombinant FanC.