bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of Leukotriene B4 receptor 1 on CD8+ T cells is essential for their migration to tumors, immune-surveillance and cancer immunity (P5106)
Authors: Sharma Rajesh , Chheda Zinal , Jala Venkatakrishna , Haribabu Bodduluri 
Published: January 2023

Abstract
The role of Leukotriene B4 (LTB4) receptor 1, BLT1 as a pro-inflammatory mediator in various inflammatory diseases is well known. However, its role in regulating immune responses to tumor is yet unknown. Here, we studied the role of BLT1 in CD8+ T cell mediated anti-tumor response using implantable TC-1 cervical cancer and B16F10 melanoma mice models. BLT1−/− mice had significantly accelerated tumor growth, reduced survival, and decreased CD8+ T cells as well as their effector molecules such as IFN-γ, granzyme-B and IL-2 within tumors as shown by flow cytometry and confocal microscopy, compared to the WT controls. Moreover, the tumor growth patterns in BLT1−/− mice was similar to WT mice that were depleted of their CD8+ T cells. Evaluation of CTL responses by in vivo killing assay revealed no differences in the cytolytic ability between WT and BLT1-/- CD8+ T cells. Adoptive transfer of tumor primed CD8+ T cells from WT but not BLT1-/- mice reduced tumor growth in Rag2-/- mice. In Rag2-/- mice, while the numbers of WT or BLT1-/- CD8+ T cells in dLN remain similar, the recruitment of BLT1-/- CD8+ T cells into tumor was dramatically reduced as compared to WT CD8+ T cells. Analysis of CD8+ T cells from the dLN revealed no difference in the expression of other T cell chemokine receptors. These results demonstrate a previously unidentified, yet crucial role of BLT1 on CD8+ T cell in their effective migration into the tumor and hence in immune-surveillance and anti-tumor immunity.
Mast cells and the Stat5 activation pathways are required for allergen-induced and spontaneous skin inflammation (P6026)
Authors: Ando Tomoaki , Xiao Wenbin , Tomimori Yoshiaki , Hong Hong , Yamashita Hirotaka , Kimura Miho , Kawakami Yuko , Kawakami Toshiaki 
Published: January 2023

Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease. Repeated epicutaneous applications of allergen (Dermatophagoides farinae extract) and staphylococcal enterotoxin B induced AD-like skin lesions on mice. We showed that this dermatitis requires mast cells and T cells, but not B cells or eosinophils, for full expression of dermatitis. The clinical severity of dermatitis was correlated with numbers of mast cells. GM-CSF, TSLPR and FcϵRI were required to attain maximal clinical scores. Moreover, high similarity was found in gene expression patterns in allergen-induced lesional skin and human AD skin, supporting the clinical relevance of our mouse model. We have also been studying spontaneously occurring AD-like skin lesions in phospholipase C (PLC)-β3-deficient mice. Mast cells, but not T or B cells, were indispensable for the development of skin lesions. Remarkable abundance of mast cells in the skin of PLC-β3-/- mice was due to the loss of an adaptor function of PLC-β3 to inhibit IL-3-mediated proliferation of mast cells via SHP-1-mediated suppression of Stat5 activity. Consistent with this, increased numbers of mast cells with phosphorylated Stat5 were found in lesional skin of PLC-β3-/- mice. Therefore, this study demonstrates a critical importance of mast cells in AD and suggests that AD development is controlled by elements of the Stat5-activating pathways, as well as other components (PLC-β3 and SHP-1) of the recently discovered multi-molecular complex SPS.
Frequent ingestion of the curry spice curcumin inhibits mastocytosis and suppresses intestinal anaphylaxis in a murine model of food allergy (P6034)
Authors: Mathias Clinton , Shah Sagar , Statham Rebecca , Gambrah Amos , Henchey Elizabeth , Schneider Sallie 
Published: January 2023

Abstract
IgE antibodies and mast cells play critical roles in the establishment of allergic responses to food antigens. Curcumin, the active ingredient of the curry spice turmeric, has anti-allergic properties, and thus may have the capacity to modulate mucosal mast cell activation and function during allergic responses. Here we show that frequent ingestion of curcumin inhibits mast cell expansion and suppresses intestinal anaphylaxis in a murine model of ovalbumin (OVA)-induced food allergy. Intragastric exposure to OVA in i.p. sensitized BALB/c mice induced a robust IgE-mediated response accompanied by enhanced OVA-IgE levels, intestinal mastocytosis, elevated serum mMCP-1 and acute diarrhea. In contrast, mice exposed to oral curcumin throughout the experimental regimen appeared to be normal and did not exhibit intense allergic diarrhea or a significant enhancement of OVA-IgE and intestinal mast cell expansion and activation. Furthermore, allergic diarrhea, and mast cell activation and expansion were also suppressed in mice exposed to curcumin during the challenge phase alone, despite the presence of normal levels of OVA-IgE. This suggested that curcumin may have a direct suppressive effect on intestinal mast cell homeostasis and function during food allergy. In summary, our data demonstrate a protective role for curcumin during allergic responses to food antigens, suggesting that frequent ingestion of this spice may modulate the outcome of disease in susceptible individuals.
Expression of ADAM10 on mast cells: effects on IgE and stem cell factor activation (P6010)
Authors: Faber Travis , Pullen Nicholas , Fernando Josephine , Kolawole Motunrayo , Barnstein Brian , Conrad Daniel , Ryan John 
Published: January 2023

Abstract
Mast cells are innate immune cells best characterized for their role in allergy. In response to cross-linking of the high-affinity IgE receptor, Fc{epsilon}RI, mast cells release mediators such as histamine, leukotrienes, IL-6, and TNF-α. Additionally, mast cells are widely noted for their secreted proteases like chymases and cathepsins. We have decided to investigate the role that the protease A Disintegrin and Metalloproteinase 10 (ADAM10) plays on murine mast cells. To date, we have discovered mast cells express ADAM10 in vitro and in vivo, and that Treg cytokines TGF-β1 and IL-10 down regulate mast cell ADAM10. IL-10 effects depend on STAT3. ADAM10 deletion results in abrogated mast cell migration through Collagen IV to stem cell factor, but not to antigen. Also, ADAM10 deletion decreases IL-6 release post cross-linking, but does not alter other commonly released cytokines such as TNF-α, IL-13, and MIP-1α. Because of these findings, we hypothesize that ADAM10 plays a pro-inflammatory role in mast cell migration and also in allergic disease.
Early growth-response 2 is critical for mast cell-directed CD4+ T cell migration via specific regulation of CCL1 production. (P6012)
Authors: Lin Tong-Jun , Wu Zhengli , MacNeil Adam , Junkins Robert , Berman Jason 
Published: January 2023

Abstract
Mast cells are well positioned in host tissue for detecting environmental signals, including allergens, leading to activation of the high affinity IgE receptor FcϵRI, and initiating a signaling cascade that perpetuates the production of biologically potent mediators including chemokines. We have identified a novel target of mast cell FcϵRI activity in the transcription factor early growth-response 2 (Egr2) and sought to characterize its function therein. Egr2 was transiently activated following FcϵRI-mediated signaling, targeted the promoter of the chemokine CCL1, and was critical for allergen-induced mast cell CCL1 production. Egr2-deficient mast cells were incapable of directing CD4+ T cell migration via the CCL1-CCR8 axis. In a model of allergic asthma, reconstitution of mast cell-deficient mice with Egr2-deficient mast cells demonstrated that mast cell Egr2 was essential for migration of CD4+ T cells to the inflamed lung. These findings position Egr2 as a critical regulator of mast cell-directed CD4+ T cell migration.
Uracil nucleotides enhance the degranulation of human basophils induced by anti-IgE antibody via a purinergic receptor (P6016)
Authors: Nakano Manabu , Kudo Fujimi , Nakamura Toshiya , Kasai Kosuke , Ito Kyoko , Takami Hideki , Ito Koichi 
Published: January 2023

Abstract
The P2Y receptors (P2YRs) are a family of G protein-coupled purinergic receptors that are stimulated by ATP, ADP, UTP, UDP, and UDP-G, and their interaction induces a wide range of biological effects in various cells through phospholipase C activation, inositol triphosphate generation, and Ca2+ release from intracellular stores. In our previous study, we demonstrated that in neutrophils, ATP regulates chemotaxis and phagocytosis via P2YR. In the present study, we examined the distribution and function of P2YR in another innate immune cell type, basophils, the degranulation of which is associated with type I allergy. To date, P2YR have been subdivided into 8 different subclasses: P2Y1, 2, 4, 6, 11, 12, 13, and 14. Of these 8 subclasses, our RT-PCR results showed the predominant expression of P2Y2, P2Y4, and particularly P2Y6, which are known as uracil nucleotide-sensitive P2YRs. Interestingly, HPLC analysis indicated that basophils spontaneously secrete UTP, the ligand for P2Y2 and 4, whereas UDP, the ligand for P2Y6, is probably generated from UTP in a metabolic pathway. Although the addition of UTP and UDP did not directly induce basophil degranulation, these nucleotides clearly enhanced the degranulation induced by anti-IgE cross-linking. These results suggest that uracil nucleotides act as potent inducers of histamine release in basophils.
Programming of immunological memory in NK cells (P1419)
Authors: Sun Joseph 
Published: January 2023

Abstract
Immunological memory is a hallmark of the adaptive immune system. Although natural killer (NK) cells have traditionally been classified as a component of the innate immune system, they share many developmental and functional similarities with B and T cells. NK cells have recently been shown in mice and humans to experience a selective education process during development, undergo a clonal-like expansion during virus infection, generate long-lived progeny (i.e. memory cells), and mediate recall responses against previously encountered pathogens - all characteristics previously ascribed only to B and T cells in mammals. The molecular events that control NK cell responses are not well understood. Using a mouse model of cytomegalovirus infection, we demonstrate that both pro-inflammatory IL-12 and type I-IFN signaling are indispensible and play non-redundant roles in the generation of virus-specific NK cell memory. Furthermore, we discovered that antigen-specific proliferation and protection by NK cells (100-1000 fold) is mediated by the transcription factor Zbtb32, which is induced by pro-inflammatory cytokines and promotes a cell cycle programme in NK cells by repressing the anti-proliferative factor Blimp-1. A greater understanding of the molecular mechanisms controlling NK cell responses will provide novel strategies for tailoring vaccines to target infectious disease.
Maternal high fat diet alters Th17 responses and bacterial colonization in newborn mice. (P3156)
Authors: Mirpuri Julie , Raetz Megan , Wilhelm Cara , Sturge Carolyn , Yarovinsky Felix 
Published: January 2023

Abstract
The American diet is dominated by high-fat foods and 50% of women of childbearing age are either overweight or obese. Studies in adult mice show that the Th17 response is important in regulating the microbiota and modulating development of diet-induced obesity. The effect of maternal high fat diet on the acquisition of the microbiota and on the Th17 cytokine responses are unknown. Objective: To define the effect of maternal high fat diet on acquisition of the microbiota and Th17 responses in offspring. Methods: 454 pyrosequencing of bacterial 16S rRNA gene in colonic fecal contents from offspring of mothers on a high fat diet and regular diet at 1-, 3-, and 6-weeks of age. Analysis of Th17 and inflammatory cytokines in the colon of offspring by qRT-PCR and ELISA. Results: 1-week-old pups from mothers on high fat diet had a unique microbiota that was dominant in Firmicutes and segmented filamentous bacteria compared to control newborn mice. Offspring of mothers on high fat diet showed a persistent change with age in their colonic microbiota even when maintained on a regular diet. There was increased production of inflammatory cytokines in pups born to mothers on high fat diet, with markedly increased expression of IL-17 and IL-22. Conclusions: Acquisition of the microbiota was unique in pups of mothers on a high fat diet with increased baseline inflammation and an altered Th17 response. Long-term consequences are under investigation and may contribute to programming obesity.
Evaluation of a mouse model of food allergy for determination of threshold oral elicitation doses (P6224)
Authors: Gangur Venugopal , Gonipeta Babu , Para Radhakrishna , Kim Eunjung , Parvataneni Sitaram 
Published: January 2023

Abstract
Food allergies are a significant public health problem because they trigger life-threatening systemic allergic reactions. We have previously reported a novel mouse model that uses transdermal exposure (TDE) to nut protein for sensitization followed by oral challenge (OC) to elicit systemic reactions. Here we evaluated the utility of this model to determine the oral threshold doses for hazelnut (HN). Groups of mice (n=8-10/group) were sensitized with 2, 3, 4 or 5 TDE to HN or saline, followed by OC with HN to induce systemic anaphylaxis. The data demonstrated that a minimum of 4 TDE to HN and a definition of &gt;/=1 o C drop in rectal temperature (RT) at 30 minutes post OC, ensures 100% positive responses and &lt;10% false positive responses. We then evaluated threshold oral elicitation doses in three scenarios: (1) homogeneous 4 TDE to allergen, followed by repeated OC with different doses of HN at weekly intervals; 2) homogeneous 4 TDE to allergen, followed by single OC per dose per group; and 3) heterogeneous (i.e., 4, 5 or 6) TDE with HN followed by single/repeated OC to simulate the human exposure conditions that are generally heterogeneous. The percent responder curves were established for each case and the NOAEL and LOAEL (25 and 50% responses) were estimated. The NOAELs were &lt;/=125 mg/Kg; the 25% response LOAELs ranged from 270-312 mg/Kg; and the 50% response LOAELs ranged from 362-412 mg/Kg.
The effect of simulated gastric and intestinal digestion on temporal stability and immunoreactivity of peanut, almond and pine nut protein allergens (P6206)
Authors: Toomer Ondulla , Do Andrew , Pereira Marion , Williams Kristina 
Published: January 2023

Abstract
Current models of digestibility utilize pepsin stability to assess the safety of allergenic versus non-allergenic food proteins. Dietary protein digestion in vivo, however, requires acid denaturation and protease cleavage by pepsin, trypsin, and/or chymotrypsin. The ability of this approach to identify food protein stability in the mammalian gut may be limited. We determined the temporal stability and immunoreactivity of almond, pine nut, and peanut allergenic proteins using simulated physiologic gastric and intestinal digestive conditions in vitro. Gel electrophoresis and immunoblot analyses were used to determine protein stability and immunoreactivity, respectively. Peanut, almond, and pine nut proteins were pepsin- and pancreatin-stable, and immunoreactive for up to 1 h after initiating digestion. Moreover, successive acid denaturation, and pepsin and pancreatin cleavage were necessary to hydrolyze these allergenic proteins and reduce their IgG and IgE-binding capacity, which suggests that digestibility models must be improved for more accurate safety assessment of food allergens.
C1q and adiponectin trigger efferocytosis via a shared pathway (P1287)
Authors: Bohlson Suzanne , Galvan Manuel 
Published: January 2023

Abstract
Failure to efficiently clear apoptotic cells (efferocytosis) is associated with autoimmunity. Complement component C1q is required for efferocytosis, and deficiency in C1q leads to development of autoimmunity. We recently identified a novel molecular mechanism for C1q-dependent efferocytosis in mouse macrophages. We found that C1q elicited the expression and function of Mer tyrosine kinase and the Mer ligand, Ga6: a receptor-ligand pair that mediates efferocytosis. To define the signal transduction pathway downstream of C1q, pathway analysis was performed using the transcriptome from C1q-treated macrophages. This analysis revealed that the adiponectin signaling pathway was significantly upregulated with C1q. Adiponectin is a well characterized adipokine with critical roles in glucose and fatty acid metabolism, and it is structurally homologous to C1q. Similar to C1q, adiponectin triggered expression of Mer that correlated with enhanced engulfment of apoptotic cells, and a soluble Mer-Fc fusion protein inhibited adiponectin-dependent efferocytosis. Furthermore, C1q triggered activation of AMP kinase, a central regulator of adiponectin signaling and cellular metabolism. Inhibition of AMPK signaling resulted in inability to upregulate C1q-dependent Mer expression in macrophages. Our results suggest that C1q and adiponectin activate macrophages via a common signaling pathway, and this pathway may contribute to the molecular crosstalk between inflammation and metabolism.
Innate immunity in pancreatic cancer patients and changes after immuno-enhancing nutrition (P1308)
Authors: Slotwinski Robert , Dabrowska Aleksandra , Lech Gustaw , Slodkowski Maciej 
Published: January 2023

Abstract
The purpose of our study was to investigate the changes of innate immunity after immunonutrition in pancreatic cancer patients. Sixty-six patients operated on for pancreatic cancer were included. Before and after preoperative nutrition TLR4,NOD1,MyD88 and TRAF6 gene expression in peripheral blood leukocytes were measured using RT Real-Time PCR. The randomized studies were performed in patients who received the pre-operative enteral nutrition (immunonutrition with glutamine or PAFAs and standard supplementation) and in patients without pre-operative nutrition. Results: TLR4, NOD1 and TRAF6 gene expressions were significantly higher (before surgery and nutrition respectively p= 0.008; 0.0008 ; 0.01) and MyD88 was significantly lower (p= 0.0002) as compared to the healthy controls. Treatment with glutamine was associated with decreased TLR4 gene expression (before versus after immunonutrition p=0.01). After PUFAs and standard nutritional support no changes in gene expressions were detected. Conclusions: Overexpression of TLR4, NOD1 and TRAF6 gene of pancreatic cancer patients may reveal the up-regulation of the innate antibacterial response. This disorders may contribute to cancer progression and increased susceptibility to postoperative septic complications. Preoperative enteral immunonutrition containing glutamine by reducing the overexpression of TLR4 gene may reduce the susceptibility of malnourished patients to post-operative septic complications.
The anti-inflammatory effects of vitamin D in mammary epithelial cells through sCD14 (P1329)
Authors: Simmons Katrina , Sellati Timothy , Welsh JoEllen 
Published: January 2023

Abstract
Many studies have shown vitamin D to regulate immune cell responses, yet few have investigated whether vitamin D alters the immune responses of epithelial cells in barrier tissues, such as the mammary gland, to alter immune signaling within tissue microenvironments. Microarray screening and qPCR of human mammary epithelial cells treated with 1α,25-dihydroxyvitamin D (the active form of vitamin D) identified CD14 as a 1,25D induced gene. To follow up these findings, we examined whether 1,25D induced the expression of membrane CD14 or soluble CD14 and found that 1,25D increased the accumulation of sCD14 in a dose- and time- dependent manner but did not alter mCD14. To determine the effects of 1,25D-induced sCD14 from HME cells on Toll-like receptor 4 activation and cytokine secretion from monocyte-derived macrophages, we incubated HEK-Blue TLR4 reporter cells and differentiated THP1 macrophages in conditioned media from 1,25D-treated HME cells ± purified E.coli lipopolysaccharide. We found that conditioned media from 1,25D-treated cells had no significant effects on TLR4 activation in HEK Blue cells yet did promote the secretion of IL-10 from differentiated THP-1 macrophages in the presence of E.coli lipopolysaccharide. These results are the first to demonstrate vitamin D’s effects on the expression and secretion of CD14 in mammary epithelial cells and support the hypothesis that vitamin D promotes an anti-inflammatory environment via secretion of sCD14 in mammary tissue.
Enhanced ICOS-L expression on DC in IL-10 deficiency and its impact on T cell subsets in respiratory tract infection (P1332)
Authors: Gao Xiaoling , Yang Jie , Yang Xi 
Published: January 2023

Abstract
Association of ICOS-L expression and IL-10 production by dendritic cells (DCs) has been commonly found in infectious disease models. The DCs with higher ICOSL expression and IL-10 production are reportedly more efficient in inducing regulatory T cells (Treg). To test whether IL-10 production and ICOS-L expression has a causal relationship, we examined ICOS-L expression by DC in IL-10 knockout (KO) mice in Chlamydia muridarum (Cm) lung infection. Moreover, we examined the development of T cell subsets, including Treg, Th17 and Th1 cell, in the condition of IL-10 deficiency and its relationship with ICOSL/ICOS signaling following infection. Surprisingly, we found that the IL-10 KO mice exhibited significantly higher ICOS-L expression by DCs. And the IL-10 KO mice showed lower Treg but higher Th17 and Th1 responses. Further analysis of Th17 and Th1 cells showed that only the Th17 response was dependent on ICOS signaling. Consistently, most of the Th17 cells were ICOS+, while most of the Th1 cells were ICOS- in the infected mice. The data suggest that ICOSL expression is independent of IL-10 production and that ICOS-L expression on DC in the presence or absence of IL-10 co-stimulation may respectively promoting Treg or Th17 response, without significant impact on Th1. The data also suggest that the enhanced protection in IL-10 KO mice may be due to the synergy of Th17 and Th1 responses.
MKK3/P38 is essential for cHSP60-induced inflammatory response (P1341)
Authors: Shi Liyun , Kang Yanhua , Wang Fang , Lu Zhe , Wang Cuili 
Published: January 2023

Abstract
Heat shock protein (HSP) 60 is the major component of Chlapidia pneumonia (C. pneumonia), and has been recognized to be related with inflammatory disorders clinically. Nevertheless, much remains to be learned about the immunopathologic property of C. pneumonia HSP60 (cHSP60). Here we report that the MAPK kinase 3 (Mkk3) is required for cHSP60-induced lung inflammation in mice, as mice with deletion of Mkk3 displayed profoundly reduced infiltration of neutrphils, production of proinflammaoty mediators, and inflammatory symptoms in lung tissue. P38 is selectively activated by Mkk3, and plays a critical role in activating production of inflammatory cytokines through transcriptional and post-transcriptional mechanisms. We also identified MSK1 to act downstream of p38 and contribute to the inflammatory response upon cHSP60 stimulation. Specific knockdown of MSK1 led to a defective phosphorylation of NF-κB/RelA at Ser276, causing the alleviated inflammatory reaction. We thus reveal the biological function of cHSP60 in vivo as well as in in vitro, and establish that MKK3/p38/MSK1 axis is essential for its pathological role, and maybe C. pneumonia-associated inflammatory diseases.