bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of long-lasting T cell memory against M. tuberculosis on vaccination with promiscuous peptide of 16 kDa antigen linked to Pam2Cys (53.11)
Authors: Agrewala Javed , Gowthaman Uthaman , Singh Vijender , Zeng Weiguang , Gupta Umesh , Jackson David 
Published: January 2023

Abstract
Tuberculosis (TB) is one of the major killer diseases, especially in developing countries. In TB-endemic areas, one of the main reasons considered for the failure of BCG (Bacillus Calmette-Guérin) is the impediment caused by environmental mycobacteria in its processing and presentation. In general, peptides do not require antigen processing since they can directly bind to major histocompatibilty complex (MHC) molecules and be presented to T cells. Consequently, vaccines constructed employing peptides can overcome the problem responsible for BCG failure. In the present study, we have developed a unique lipopeptide by linking the promiscuous peptide of 16 kDa antigen of Mycobacterium tuberculosis to Pam2Cys, a toll like receptor-2 (TLR2) agonist. This peptide elicits immune response irrespective of HLA polymorphism. Further, it does not require extensive antigen processing, can bind directly to MHC molecules and activate T cells. Most interestingly it has self-adjuvanting properties and activates both innate and adaptive arms of immunity. Further, it activates dendritic cells (DCs) and imparts enduring Th1 memory response. Furthermore, it surmounts the barrier of MHC polymorphism and induces better protection than BCG. This lipopeptide can be a potent future vaccine candidate against TB.
Selection of conserved HIV-1 vaccine epitopes based on cross-reactivity to feline immunodeficiency virus (53.17)
Authors: Sanou Missa , Coleman James , Levy Jay , Yamamoto Janet 
Published: January 2023

Abstract
Recent reports suggest that CTLs against the conserved epitopes on HIV-1 are required for an effective HIV-1 vaccine, and that the vaccine should induce CTLs to conserved epitopes mimicking those generated by HIV-1+ long-term survivors (LTS). The CTL epitopes needed for vaccine are still unclear. Our current study identifies the evolutionarily-conserved CTL epitopes preserved between HIV-1 and FIV reverse transcriptases (RT) most frequently recognized by HIV+ subjects, including LTS. The IFNγ-ELISpot, CFSE-proliferation, and intracellular staining (ICS) analyses of PBMC upon stimulation with HIV or FIV RT peptide pools or peptides (overlapping 15-mer peptides of whole RT) were used to map the anti-FIV and anti-HIV responses made by HIV+ group (n=14 includes 7 LTS) and HIV- controls (n=5). The HIV+ subjects had HLA alleles from 8 supertypes (mainly A2 supertype) and some with B57 or B27 allele for AIDS nonprogression. Seven of 14 HIV+ subjects (includes 4 LTS) reacted to 4 FIV RT pools and to their HIV counterparts, and none by the controls. Peptides from these pools induced the proliferation of CD3+CD8+ or CD3+CD4+ T cells, which were ICS positive for IFNγ, perforin, granzyme-A, or granzyme-B in various combinations. The existence of evolutionarily-conserved CTL epitopes was determined using HIV/FIV epitope mapping. This approach can select for highly conserved epitopes that are less likely to mutate and as a result can be useful in the development of an HIV-1 vaccine.
Specific regions of the ricin toxin A subunit are involved in eliciting protective antibodies: implications for vaccine design (53.5)
Authors: O'Hara Joanne , Brey Robert , Mantis Nicholas 
Published: January 2023

Abstract
Efforts to develop an effective vaccine against ricin are focused on engineering attenuated and stable recombinant forms of the toxin’s enzymatic A subunit (RTA). While several candidate antigens are in development, vaccine design and efficacy studies are being undertaken in the absence of a fundamental understanding of the regions of RTA that are critical in eliciting protective immunity. To address this issue, we recently identified six distinct immunodominant linear regions on RTA. Using monoclonal antibodies (MAbs) specific to each region, we determined that protective antibodies were directed against α-helices located in RTA folding domains 1 and 2, whereas non-neutralizing antibodies recognized random coils and loops that were primarily confined to folding domain 3. This suggests that neutralizing and non-neutralizing antibodies target distinct domains on RTA. In support of this hypothesis, we now report that the vast majority of conformation-dependent ricin neutralizing MAbs bind to RTA 1-33/44-198, a recombinant RTA deletion mutant lacking folding domain 3. Furthermore, preliminary studies in mice suggest that RTA 1-33/44-198 is more effective than an attenuated RTA point mutant at eliciting neutralizing antibodies. These data offer insights into the immunodominant and structural determinants on RTA that give rise to protective immunity, and for the first time provide an immunological rationale for ricin vaccine design.
Anti-inflammatory activity of Dioscoreae rhizome in macrophages by inhibition of pro-inflammatory cytokines via NF-κB signaling pathway (54.11)
Authors: Kim Seulah , Shin Seulmee , Park Yoonhee , Lee Seungjeong , Lee Chong-Kil , Kim Kyungjae 
Published: January 2023

Abstract
Dioscoreae rhizome (DR) has been used in traditional medicine to treat numerous diseases and reported to have anti-diabetes and antitumor activities. The pharmacological and biochemical mechanisms of the water extracts of DR (EDR) on macrophages in immune responses have not been clearly elucidated. We examined whether EDR suppresses the production of pro-inflammatory cytokines and the expression of co-stimulatory molecules. EDR reduced the production of NO and PGE2 through the suppressed gene and protein expression of iNOS and COX-2 in the both RAW 264.7 cells and peritoneal macrophages. The production of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 production were suppressed by EDR. The change of gene expression by EDR treatment was analyzed by using RT-PCR, and the associated mRNA expression was inhibited same as cytokine production. Western blot analysis showed the augmentation of cytokine related protein on EDR treatment whereas anti-inflammatory cytokines, IL-4 and IL-10, did not significantly change. The expression level of co-stimulatory molecules such as ICAM-1, B7-1, and B7-2 also was reduced with the increment of EDR concentration. The nuclear translocation of NF-κB activity in LPS-activated macrophages was suppressed by EDR. These results showed EDR decreased pro-inflammatory cytokines via the inhibition of NF-κB dependent inflammatory protein level and suggesting that how EDR could be useful immunomodulatory agent for treating immunological diseases.
The immunological ménage à trois promotes inflammation in Type 2 diabetes. (54.14)
Authors: Bogdan Madhumita , McDonnell Marie , Shin Hyunjin , Rehman Qasim Rehman , Hasturk Hatice Hasturk , Apovian Caroline , Nikolajczyk Barbara 
Published: January 2023

Abstract
Type 2 diabetes (T2D) is an inflammatory disease promoted by changes in immune cell function. Monocytes and T cells play roles in T2D inflammation as evidenced, in part, by our demonstration of pro-inflammatory T cell subset skewing in T2D patients. However, the role of cross-talk amongst immune system cells in T2D is poorly unstudied. PBMC depletion studies showed that T2D patient T cells, unlike non-diabetic (ND) donor cells, required monocytes to maintain IL-17 hyper-secretion. In contrast, B cell depletion did not affect T2D Th17 function, but surprisingly, B cell depletion from non-diabetic (ND) mixed cell cultures significantly elevated Th17 function. Based on the role B cell IL-10 plays in inflammation resolution, we tested the hypothesis that IL-10 regulates immune cell cross-talk to block Th17 function. IL-10 addition to B cell-depleted PBMCs decreased IL-17 to “healthy” levels in both ND and T2D samples, indicating that both cell types are physiologically capable of interpreting the anti-inflammatory signals from B cells despite the presence of pro-inflammatory monocytes in T2D samples. Critically, unlike ND B cells, T2D B cells fail to secrete IL-10, thus lack of B cell IL-10 in T2D samples compounds elevated pro-Th17 cytokine production by monocytes. We conclude that IL-10 can block monocyte-mediated increases in Th17 function, and that lack of B cell IL-10 in T2D associates with IL-17-induced inflammation thus metabolic imbalance.
Anti-inflammatory and anti-bacterial effect of polyacetylene compound from Cirsium japonicum var. ussuriense (54.19)
Authors: Lee Ki-Man , Lee Geum Seon , Yim Dongsool , Kim Kyungjae , Kang Tae Jin 
Published: January 2023

Abstract
Cirsium japonicum var. ussuriense is known to have a variety of biological activities, including anti-inflammatory, analgesic activity and antipyretic activity. The role of 1-Heptadecene-11, 13-diyne-8, 9, 10-triol (PA), a polyacetylene compound isolated from the root of Cirsium japonicum var. ussuriense was herein investigated as an inhibitor of some macrophage functions involved in the inflammatory process. The effect of PA on the production of pro-inflammatory cytokines, interleukin-1beta (IL-1β) and tumour necrosis factor-alpha (TNF-a), and nitric oxide (NO) were tested in mouse macrophage cell line, RAW264.7 by ELISA method and griess reaction, respectively. PA inhibited lipopolysaccharide (LPS)-induced IL-1β and TNF- a production by macrophages at a dose dependent manner. PA also supressed inhibited the NO production of macrophages by LPS. LPS-induced NF-kB activity was decreased by treatment of PA. Next, anti-bacterial activity of PA with E. coli and S. aureus was maesured by MIC (Minimum Inhibitory Concentration). PA significantly inhibited bacterial growth. Therefore, these results indicated that PA has anti-inflammatory and anti-bacterial activities.
Eph receptors are involved in the pro-inflammatory response following spinal cord injury (54.21)
Authors: Glass Stephanie , Theus Michelle , Zhuang Zhiye , Liebl Daniel 
Published: January 2023

Abstract
Following spinal cord injury (SCI), residential microglia and astrocytes in the spinal cord are known to activate an innate immune response. Here, we examined a role for EphB3 and EphA4 receptors in the early immune response following SCI. Our results demonstrate that EphB3 and EphA4 are present on both microglia and astrocytes in the adult spinal cord, and that they are phosphorylated within 15 min after the initiation of injury. Receptor activation by the ligand ephrinB3 is thought to enhance multiple cytokine mRNA transcripts involved in the immune response, as well as mediate the release of several pro-inflammatory cytokines in vitro. These responses are significantly attenuated in cells derived from mice deficient for EphB3 and EphA4. Interestingly, analysis of the whole spinal cord, using ELISA Assay, showed a significant attenuation in interleukin-6 (IL-6) in astrocytes but not microglia derived from EphB3/EphA4 double knockout (EphB3/A4-/-) mice. To examine cytokine levels following SCI, we collected spinal cord tissues from sham or SCI wild type (WT) and EphB3/A4-/- mice at 4 and 24 hours and analyzed cytokine levels using cytometric bead array. We observed a significant increase in IL-6 and chemokine ligand 2 (CCL-2) at 4 and 24 hours post-SCI in WT but not EphB3/A4-/- mice. These data suggest a novel role for EphB3 and EphA4 in the early activation of the acute immune response, and possibly the progression of damage to the injured spinal cord.
Predominant role of monocytes rather than neutrophils in the pathogenesis of the familial autoinflammatory disease TRAPS (TNFR-associated Periodic Syndrome) (54.3)
Authors: Pelletier Martin , Bulua Ariel , Myerowitz-Vanderhoek Samuel , Kastner Daniel , Siegel Richard 
Published: January 2023

Abstract
Mutations in the type 1 TNF receptor (TNFR1) cause the autoinflammatory disorder TNF receptor-associated periodic syndrome (TRAPS), a disease characterized by recurrent fevers with inflammation. TRAPS-associated mutations in TNFR1 cause misfolding, retention in the ER, and loss of function as a conventional receptor, but instead initiate an intracellular signaling cascade that results in hyper-responsiveness to innate stimuli. Using mice engineered to have TRAPS-associated mutations in TNFR1, we examined the contents of peritoneal lavage fluid after intraperitoneal LPS injection in order to identify the pathogenic cell type. TNFR1 mutant mice have increased monocyte/macrophage infiltrates when compared to wild-type mice, but a similar number of recruited neutrophils. In mixed marrow chimeras, wild-type and TNFR1 mutant neutrophils were recruited similarly into the peritoneum after LPS injection, suggesting that there is no cell-intrinsic predisposition of TNFR1 mutant neutrophils to accumulate at sites of inflammation. In support of this, neutrophils from TRAPS patients and healthy donors migrate similarly in response to CXCL8. In contrast, we found that murine peritoneal macrophages from TNFR1 mutant mice produce higher amounts of two potent chemokines, CXCL1 and CXCL2, in response to LPS in vitro. These results suggest that enhanced chemokine secretion by monocytes, rather than hyper-responsiveness of neutrophils to these stimuli, is critical to the pathogenesis of TRAPS.
A role for periostin in regulation of goblet cell metaplasia (55.1)
Authors: Sehra Sarita , Nguyen Evelyn , Snider Paige , Petrache Irina , Conway Simon , Kaplan Mark 
Published: January 2023

Abstract
Periostin is a 90kD member of the fasciclin-containing family and functions as part of the extracellular matrix. Periostin is expressed in a variety of tissues and expression is increased in airway epithelial cells from asthmatic patients. Recent studies have implicated a role for periostin in allergic eosinophilic esophagitis. To further define a role for periostin in Th2-mediated inflammatory diseases such as asthma, we studied the development of allergic pulmonary inflammation in periostin-deficient mice. Sensitization and challenge of periostin-deficient mice with ovalbumin resulted in increased peripheral Th2 responses compared to control mice. In the lungs, periostin-deficiency resulted in increased airway resistance and significantly enhanced mucus production by goblet cells concomitant with increased expression of Gob5 and Muc5ac, compared to wild type littermates. Importantly, the physiological significance of the function of periostin is demonstrated by its ability to inhibit the expression of Gob5, a putative calcium-activated chloride channel involved in the regulation of mucus production, in primary murine airway epithelial cells. Our studies suggest that periostin may be part of a negative-feedback loop regulating allergic inflammation that could serve as a therapeutic target in the treatment of atopic disease.
Itk negatively regulates IFNγ, influencing T helper 2 response in vivo (55.16)
Authors: Kannan Arun , Sahu Nisebita , August Avery 
Published: January 2023

Abstract
Asthma is a major public health concern affecting millions of people each year. Allergic asthma is a T helper 2 (Th2) cell mediated inflammatory disease characterized by airway inflammation and hyper responsiveness. The Tec family tyrosine kinase Interleukin-2 Inducible T cell kinase (Itk) is primarily expressed in T cells and is critical for development, function and differentiation of T helper cells. Itk-/- mice have a defective Th2 response and are not susceptible to allergic asthma and parasitic worm infections. We observed that naïve CD4+ T cells from Itk-/- mice have substantially increased transcript levels of prototypic Th1 genes. We hypothesized that this upregulation of Th1 genes could negatively regulate polarization to Th2 effector cells. Here, we show that Itk can negatively regulate IFNγ. More importantly, in absence of IFNγ there is a rescue in the expression of Th2 related genes and Th2 mediated allergic asthma in Itk-/- mice. In the absence of Itk, IFNγ levels increase leading to a positive feed-forward loop with T-bet. This is responsible for the inability of CD4+ T cells from Itk-/- mice to optimally induce Th2 transcriptional program and develop a Th2 response upon allergen challenge. In addition to providing mechanistic insight into the observed Th2 defects in Itk-/- mice, this work has implications for understanding Itk as a potential target for Th2 mediated inflammation, T helper differentiation programs and the molecular pathology of asthma.
Effects of electroacupucture at ST36 point on regulatory T cells in a murine model of OVA-induced allergic asthma (55.18)
Authors: Youngjoo Kwon , Kim Youngeun , Lee Gihun , Ham Gyeonggeun , Shin Minkyu , Hong Moochang , Bae Hyunsu 
Published: January 2023

Abstract
Allergic diseases, including asthma, are defined as chronic inflammatory disorders originating from an aberrant immune response to innocuous antigens. Current therapies are effective in crosssections of patients, but remain mostly palliative. Given the capacity of regulatory T cells (Tregs) to suppress disease-promoting immune responses, enhancing Treg function represents an attractive therapeutic strategy for the treatment of allergic disease. Among the complementary therapeutic approaches to asthma, acupuncture has been widely used and its efficacy has been well-known. The selected acupoint was ST36, as it is considered of choice to treat asthma. This study was conducted to address not only EA treatment reduce allergic inflammatory processes, but also to observe whether these beneficial effects of EA on asthma could be correlated with CD4+CD25+ regulatory T cells. EA treatment began 7 days after antigen priming and was repeated for 10 consecutive days. Cellular profiles and histopathologic analysis demonstrated that peribronchial and perivascular inflammatory cell infiltrates were significantly lower in control and EA groups compared to OVA and Treg depletion groups. Additionally, the population of CD4+CD25+Foxp3+ in lung cells increased in EA groups, compared to OVA. These results imply that EA at ST 36 efficiently diminishes the bronchial immune-mediated inflammation and that these effects might correlate to regulatory T cells.
Allergic experimental asthma can be ameliorated by allergen specific immunotherapy in the absence of T-bet. (55.6)
Authors: Böhm Livia , Übel Caroline , Maxeiner Joachim , Dehzad Nina , Heinz Anke , Martin Helen , Reuter Sebastian , Schild Hansjörg , Taube Christian , Finotto Susetta 
Published: January 2023

Abstract
Clinical studies have demonstrated that repeated subcutaneous (s.c.) administrations of allergen are effective in the treatment of allergic diseases. It has been suggested, that the success of this treatment, also known as allergen specific immunotherapy (IT), relates to a shift of the T helper 2 (Th2) to T helper 1 (Th1) cells, a blockade of specific antibodies and/or the induction of regulatory T cells (Treg). The T box transcription factor (T-bet) is crucial for the Th1 development and previous studies demonstrated that T-bet deficient mice (T-bet KO) develop a severe asthmatic phenotype. Thus we address the question of whether T-bet is necessary for the effectiveness of IT. T-bet KO mice were analyzed in a murine model of allergic airway disease and IT. OVA-sensitized T-bet KO or BALB/c mice were treated with 3 s.c. injections of OVA (1000µg/injection) prior to airway challenge. This treatment was effective in suppressing the allergen-induced asthma manifestations such as airway hyperresponsiveness (AHR), serum IgE, lung eosinophilia and airway inflammation in sensitized and challenged wildtype mice. Consistently Th2 cytokines were reduced in the lung of IT treated mice. IT treated T-bet KO mice showed an alleviated airway disease following IT to a comparable degree as that observed in the wildtype mice. In summary, the present study shows that IT is not dependent on T-bet and that this treatment effectively suppresses the development of AHR and airway inflammation.
Borrelia burgdorferi pathogenic potential correlates with type I and type III IFN production by human immune cells. (56.18)
Authors: Krupna Michelle , Wormser Gary , Schwartz Ira , Petzke Mary 
Published: January 2023

Abstract
Borrelia burgdorferi (Bb) is the extracellular bacterial agent of Lyme disease. Bb elicits type I interferon (IFN) in humans via Toll-like receptors 7 and 9. Bb clinical isolates with different pathogenic potential were tested for their ability to induce IFNs in human peripheral blood mononuclear cells (PBMCs). Disseminating Bb isolates induced significantly higher levels of both type I (IFN-α) and type III IFN (IFN-λ) than did non-disseminating Bb isolates. In contrast, there was no significant difference in type II IFN (IFN-γ) production, nor in levels of IL-2, 6, 8, 10. However, non-disseminating Bb isolates induced significantly higher levels of TNF-α and IL-1β. In addition, disseminating clinical isolates were able to directly induce multiple IFN-responsive genes; non-disseminating strains required IFN-feedback signaling. A mutant of Bb was identified that was unable to induce a robust IFN-α response when compared to wild-type (wt); IFN-γ levels were not affected. Wt and mutant Bb were GFP-tagged and assessed for their ability to be phagocytosed by human immune cell populations using flow cytometry and fluorescence microscopy. There were more wt than mutant Bb associated with (p=0.01) and internalized by (p=0.034) PBMCs. These findings suggest that disseminating and non-disseminating clinical isolates may be differentially phagocytosed by dendritic cells. Intriguingly, the differential uptake appears to be mediated by factor(s) encoded on a single linear plasmid of Bb.
CD74 deficiency is protective against P. aeruginosa-induced ocular keratitis (56.20)
Authors: Gadjeva Mihaela 
Published: January 2023

Abstract
Eye trauma and contact lens wear are the main factors that predispose to the development of infectious keratitis. The existing therapy often fails to control the excessive tissue damage that is induced during P. aeruginosa infection. While antibiotic treatment can reduce the bacterial burden, tissue damage occurs as a result of exaggerated local inflammation. Thus, a combined therapy including agents that control local inflammatory responses could be highly beneficial. We report that deficiency for CD74, the invariant chain for MHCII, appears protective against P.aeruginosa-induced corneal damage. This protection is exemplified with reduced bacterial burdens, and reduced pathology during infection. Since CD74 deficiency impairs MHCII-driven antigen presentation, changes in the CD4+ T cell maturation are expected. Consistently, the observed improved recovery of the CD74 KO could be due to alterations of the CD4+ T cell functions. However, about 8-10% of the CD74 is expressed on the cell surface, independently of the MHCII, where it forms complexes with CD44, and serves as s receptor for macrophage migration inhibitory factor (MIF). An alternative scenario to explain the lessened pathology would be a deficiency in the MIF-CD74 signaling axes. Consistently, MIF deficient mice are protected from P.aeruginosa-induced karatitis, suggesting that MIF-driven CD74-mediated activities exacerbate pathology during acute bacterial infection.