bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Quantum Dots Nanoparticles on Caenorhabditis elegans infected with Microsporidia
Authors: Elfert Amr , Meiner Kavan , Idris Sally , Cotlet Mircea , Delaney Tetyana 
Published: January 2023

Abstract
Caenorhabditis elegans are model organisms that have intestinal lining similar to that of humans. They are transparent and can be easily cultivated in the lab. Nematocida parisii is an intracellular parasitic species of microsporidia that infect the intestines of C. elegans. Similar species cause microsporidiosis in humans. Microsporidiosis can cause severe digestive system symptoms including life-threatening diarrhea in immunocompromised as well as in immunocompetent individuals. Currently available treatments are not always sufficient and can be toxic.
In this experiment, the effects of different nanoparticles (NPs) on the intestinal lining of C. elegans and N. parisii within are tested. It was reported that NPs can diffuse through cellular membranes and cause oxidative stress, DNA damage, and macrophage activation. Some NPs showed anti-bacterial and anti-fungal effects.
If the treated C. elegans have a longer lifespan and a larger population density than untreated ones, then NPs can preferentially diffuse through the epithelial cells of the intestines and affect the infection. The number of thrashes of the C. elegans was used as a measure of their response to stimuli. Irritating and disrupting stimuli cause an initial increase in the movements but it is then followed with a sharp drop and the organisms may eventually die. The imaging of C. elegans was done using confocal microscopy with DIC. The preliminary results showed that the quantum dots of 655 nm emission wavelength and at a concentration of 0.8μM showed no significant difference that indicated a harmful effect on the C. elegans. Thus, different concentrations and longer exposure times will be implemented to compare their effects on the microsporidia.
MicroRNA-146a limits tumorigenic IL-17-mediated inflammation in colorectal cancer
Authors: Garo Lucien Peter , Ajay Amrendra K , Fujiwara Mai , Gabriely Galina , Raheja Radhika , Gopal Murugaiyan 
Published: January 2023

Abstract
Interleukin-17 (IL-17) is a major inflammatory cytokine implicated in colorectal cancer (CRC) development. However, the mechanisms that control tumorigenic IL-17 signaling remain unclear. Recently, expression changes and polymorphisms in the small non-coding RNA, microRNA-146a (miR-146a), have been associated with clinical outcomes in inflammatory bowel disease and CRC patients. Here, we identified a novel role for miR-146a as a major negative regulator of colonic inflammation and tumorigenesis via modulation of IL-17 responses. MiR-146a-deficient mice are highly susceptible to both colitis-associated and sporadic CRC, and present with enhanced tumorigenic IL-17 signaling. Within myeloid cells, miR-146a targets RIPK2, an intermediate in NOD2 signaling, to limit myeloid cell-derived IL-17-inducing cytokines and restrict colonic IL-17 levels. Accordingly, myeloid cell-specific deletion of miR-146a leads to CRC susceptibility. Moreover, within intestinal epithelial cells (IECs), miR-146a targets TRAF6, an intermediate in IL-17R signaling, to restrict IEC responsiveness to IL-17. MiR-146a within IECs further suppresses CRC by targeting PTGES2, an enzyme for PGE2 synthesis. IEC-specific deletion of miR-146a therefore confers marked CRC susceptibility. Importantly, preclinical administration of miR-146a mimic can ameliorate colonic inflammation and CRC. In conclusion, miR-146a prevents CRC by two interlinked mechanisms: 1) by limiting myeloid cell-mediated inflammatory IL-17 production; and 2) by inhibiting tumorigenic IL-17R signaling in IECs. Overexpression of miR-146a may be a promising therapeutic approach for CRC to limit multiple pathways converging on tumorigenic IL-17 signaling.
B cells produce anti-inflammatory cytokine IL-27 in the gut upon induction by cyclic dinucleotides and to prevent murine colitis
Authors: Wu Shuai , Yan Hui , Rivera Carlos Eduardo , Wang Jingwei , Fernandez Maria , Li Xiaodong , Wang Xiaoyan , Xu Zhenming 
Published: January 2023

Abstract
In addition to differentiating into plasma cells that secrete microbiota-shaping protective IgA antibodies, B cells may function as regulatory cells that are induced to produce cytokines to maintain gut integrity. In mouse gut-associated lymphoid tissues and mesenteric lymph nodes, B cells were the primary source of IL-27 in homeostasis and upon induction by dextran sulfate sodium (DSS)-elicited intestinal injury. Production of pleiotropic cytokine IL-27 (EBI3/p28) by B cells was dependent on their expression of STING, consistent with the ability of cGAMP, the cyclic dinucleotides (CDNs) product of cGAS upon sensing DNA, to prime B cells for IL-27 induction by CD154. Furthermore, B cell-specific deficiency in IL-27 (but not IL-35) or STING in DSS-treated mice resulted in specific impairment in generating plasma cells and T-bet+NCR+ Group 3 innate lymphoid cells (ILC3s), reduced IgA secretion into the gut lumen and expression of anti-inflammatory IL-22 (and concomitant increase in pro-inflammatory IL-17, as produced by T-bet−NCR− ILC3s) and severe colitis-like symptoms. These, together with the ability of IL-27-producing B cells generated in vitro by cGAMP priming and CD154 stimulation to prevent lethality caused by sustained DSS treatment, show that B cells in the gut respond to immunoactive CDNs to induce IL-27 for the maintenance of intestinal homeostasis.
Microbial hydrogen economy alleviates colitis by reprogramming colonocyte metabolism and reinforcing intestinal epithelial barrier
Authors: Ge Li , Qi Jie , Sun Xueqiang , Liu Shuman , Li Pengfei , Chen Hao , Shao Bo , Wang Shiyang , Ruan Zhenzhen , Song Wengang 
Published: January 2023

Abstract
Several studies have found exogenous H2 treatment can alleviate inflammatory damage in inflammatory bowel disease (IBD) animal models, but the mechanisms behind it are less clearly understood. The present study aimed to investigate whether hydrogen-rich saline (HS) attenuates IBD in mice model and the underlying mechanisms. The results showed that HS administration significantly inhibit weight loss and reduce inflammatory damage in dextran sulfate sodium (DSS)-induced acute ulcerative colitis (UC) mice model. We observed that H2 regulates the composition of microbiota by up-regulating the abundance of intestinal specific short chain fatty acids (SCFAs)-producing bacteria. Increased butyrate-producing microbes activated the intracellular butyrate sensor peroxisome proliferator–activated receptor γ (PPAR-γ) signaling pathway, meanwhile decreased the epithelial expression of Nos2, the gene encoding inducible nitric oxide synthase, and thus promoted the recovery of colonic anaerobic environment. Our results also indicated that HS administration reduce intestinal epithelial barrier permeability by decreasing the dextran concentrations in serum, inhibit dysbiotic Enterobacteriaceae expansion, increasing mucus secretion in the colonic lumen, and promoting the expression of intestinal interepithelial tight junction protein. Taken together, we identified the mechanism by which exogenous H2-improved “microbial hydrogen economy” regulates metabolic reprogramming of colonocyte through microbiota-activated PPAR-γ signaling pathway to provide colonic anaerobic environment, and reinforces intestinal epithelial barrier function, thereby promoting the recovery of intestinal homeostasis.
Efferocytosis mediated by TAM receptors maintains lung homeostasis and controls inflammation in a mouse model of silicosis
Authors: Pinto Kamila Guimaraes , Ferreira Antonia Castro , Leandro Monique , Lopes Marcela F , Vazquez Estefania , He JianPing , Kelsall Brian L , Filardy Alessandra 
Published: January 2023

Abstract
Alveolar macrophages (AMs) are key cells for the establishment of pulmonary homeostasis. Efferocytosis is one of the main regulatory mechanisms for maintaining tolerance and homeostasis. The TAM receptor family (Tyro3, Axl and MerTk) mediates efferocytosis and inhibits proinflammatory pathways through Gas6 or Protein S binding to phosphatidylserine on apoptotic cells. Here we investigated how lung macrophages are regulated by TAM receptors in homeostasis and during silicosis. We found that LPS-stimulated AMs have an impaired ability to secrete IL-1b, IL-6, IFN-b, and MCP-1, but produce high levels of TNF-a and lower levels of IL-10, compared to bone marrow derived macrophages (BMDM). During homeostasis, AMs from wild type (WT) mice showed high expression of Axl, MerTk, and Gas6 by RT-PCR. Compared to WT mice, Axl−/− and MerTk−/− mice had more airway cells, less TGF-b and IL-10, and higher levels of IL-17 and KC within BAL. In addition, both KO mice had a higher frequency and number of AMs in the BAL, and secreted high levels of MCP-1, IFN-b, GM-CSF, and IL-10 following LPS stimulation compared to WT mice. Fifteen days after intra-tracheal silica instillation (SiO2; 20 mg), Axl−/− and MerTk−/− mice lost more body weight, and had increased lung weight, and percentage and number of neutrophils in the BAL compared to WT mice. Furthermore, both KO mice had a decreased percentage of AMs, and higher levels of KC, TNF-α and TGF-β but lower levels of IL-10 in the BAL compared to WT mice. Finally, Axl−/− mice had higher levels of IL-1β and IL-6 in the BAL than MerTk−/− mice. Our data suggest that efferocytosis mediated by Axl and MerTk receptors plays an important role in maintaining homeostasis and controlling inflammation in the pulmonary mucosae.
Do inflammasomes play a role in controlling cell damage/injury (ARDS) in order to initiate the cascade of healing and tissue repair?
Authors: Lau Jenny May-Sim , McKay Emma , Curran Joseph , Bertholon Tara , Krasnodembskaya Anna , Ingram Rebecca , Fitzgerald Denise , O’Kane Cecilia , Dombrowski Yvonne 
Published: January 2023

Abstract
Inflammasomes are cytosolic multiprotein complexes that assemble in response to various stimuli. Activated inflammasomes process pro-IL-1β and pro-IL-18 into bioactive forms. inflammasome-derived IL-1β initiates epithelial cell and fibroblast proliferation. Thus, inflammasomes might also be decisive key drivers through activating and recruiting cells required for efficient tissue repair. However, their exact function in lung tissue damage and repair are unclear. C57BL/6, NLRP3−/− and Caspase1/11−/− mice were treated with 40μg LPS by intratracheal instillation to induce lung injury. Lungs and BALF were collected for histological scoring, cytokine analysis and inflammasome marker expression by IHC, immunoblotting and ELISA. The Lung injury score of LPS treated mice was increased on day 1 and 3 but reverted to nearly normal on day 7. NLRP3 deficiency did not alter lung damage indicating that the NLRP3 inflammasome might not be an essential mediator of injury in this model. LPS induced lung epithelial type 2 cell damage was shown by decreased Pro-SPC expression, which was associated with increased expression of inflammasome markers (ASC, NLRC4, and NLRP3) and pro-IL-1β. Immune cells and more specifically CD68+ macrophages and Ly6G/C+ neutrophils were the predominant cell types expressing inflammasome markers. Caspase1/11−/− mice had reduced IL-1β levels in BALF compared to LPS-treated C57BL/6 mice indicating a potential role of inflammasomes in response to tissue damage. However, both NLRP3−/− and caspase1/11−/− mice had no significant change in CXCL1/KC levels in BALF compared to C57BL/6 mice on Day 3 and 7 of the acute lung injury model. Further investigations will reveal the impact of inflammasome activity on tissue repair.
Effects of E-Cigarette Vapor on the Pulmonary Immune System
Authors: Poindexter Morgan E , Laing Emilia , Singhrao Navid , Li Xiaohan , Pinkerton Kent E. 
Published: January 2023

Abstract
E-cigarettes are nicotine delivery devices that have rapidly gained popularity in recent years. It is not well understood how the use of these devices impact the pulmonary immune system and its ability to defend against respiratory viral infection. To this end, BALB/c mice were exposed to e-cigarette aerosols for 3 hours per day, 5 days per week for 2 weeks. Lung tissue and serum were collected following 1, 3, 5 and 10 days of exposure. Average serum nicotine and cotinine concentrations during the 10-day exposure were 133 ± 46 ng/mL and 712 ± 302 ng/mL, respectively, which is consistent with levels found in active tobacco smokers. Compared to filtered air controls, e-cigarette exposure significantly increased total cells and macrophages in bronchoalveolar lavage fluid on days 1 and 5, and significantly decreased neutrophils on day 1, suggesting that e-cigarette vapor may change the cellular infiltrate of the lungs. mRNA expression of IL-1β, IL-6, TNFα and IL-10 in right lung tissue was significantly decreased at all timepoints, suggesting possible dampening of the pulmonary immune response. To investigate how these cellular changes may effect the response to viral stimuli, human Type II epithelial cells were treated with e-cigarette conditioned media 24 hours prior to poly(I:C) stimulation. Compared to controls, e-cigarette treatment of type II epithelial cells resulted in significantly decreased expression of the critical interferon pathway genes IRF3, IFNα, and IL-1β following poly(I:C) stimulation. E-cigarette media alone was able to significantly decrease the expression of IRF3 in these cells, suggesting e-cigarette vapor may impair key genes necessary for the recognition of and sufficient response to respiratory viruses.
Anti-dsDNA specific antibody secreting cells are increased in both frequency and abundance in Chronic Rhinosinusitis with Nasal Polyps
Authors: Bai Junqin , Hulse Kathryn E. , Huang Julia , Schleimer Robert P. , Tan Bruce K. 
Published: January 2023

Abstract

Background
We have previously found that anti-dsDNA IgG autoantibodies are increased in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) patients. Recent studies find that B cells with the Epstein-Barr virus-induced protein 2(EBI2), is critical to the extrafollicular response. We have described elevated numbers of EBI2+ B cells in NP and they were more frequently antibody secreting cells (ASCs). In this study we evaluate whether dsDNA-specific ASCs are increased in NP and further compared the EBI2+ and EBI2− compartments.

Methods
To investigate this problem, flow cytometry and ELISpot assays were utilized to compare the frequency of total IgG and dsDNA specific IgG ASCs and cells were sorted into EBI2+ and EBI2− B cells from human NP and tonsils.

Results
Flow cytometry results (n=10 tonsil, 4 NP) found that although tonsils had significantly more B cells than NP, a significantly smaller proportion were CD27+CD38+ plasmablasts (PB). Further ELISpot analysis found NP B cells were more frequently IgG ASCs than tonsil (0.06% and 0.43% in tonsil (n=9) and NP (n=5) respectively, p&lt;0.001). Anti-dsDNA specific ASCs were two-fold more in NP representing 0.95% of IgG ASCs compared with 0.4% in tonsil ASCs (p&lt;0.05). In analysis of ASCs sorted from tonsils (n=3) and NP (n=2), we found anti-dsDNA IgG ASCs were more frequent among EBI2+ compared to EBI2− cells with 10- and 14-fold increases in dsDNA reactivity (p&lt;0.01).

Conclusions
Although B-cells are significantly more abundant in tonsils, NP derived B-cells more frequently secrete total- and dsDNA-specific IgG. These differences appear to be driven by extrafollicular EBI2+ B-cells suggesting that EBI2+ B cells represent the major pool of autoreactive B-cells observed in CRSwNP and tonsils.
Airway mucociliary dysfunction enhances antigen-specific nasal IgA immune responses to cholera toxin-based nasal vaccine
Authors: Lan Huangwenxian , Suzuki Hidehiko , Nagatake Takahiro , Hosomi Koji , Ikegami Koji , Setou Mitsutoshi , Kunisawa Jun 
Published: January 2023

Abstract
Nasal mucosal tissues are equipped with physical barriers, mucus and cilia, on their surface. The mucus captures inhaled materials, and the cilia remove the captured materials from the epithelial layer by asymmetrical beating. Effect of nasal physical barriers on the vaccine efficacy remains to be investigated. Tubulin tyrosine ligase-like family member 1 (Ttll1) is an essential enzyme for appropriate movement of the cilia on respiratory epithelium, and its deficiency (Ttll1-KO) leads to the impaired asymmetrical beating of cilia and consequent mucus accumulation in the nasal cavity. Here, when mice were intranasally immunized with pneumococcal surface protein A (PspA) together with cholera toxin, Ttll1-KO mice showed higher levels of PspA-specific IgA in the nasal wash and increased numbers of PspA-specific IgA-producing plasma cells in the nasal passages when compared with Ttll1 hetero (He) mice. Mucus removal by N-acetylcysteine did not affect the enhanced immune responses in Ttll1-KO mice. We further found that retention time of PspA in the nasal cavity in Ttll1-KO mice was longer than that in Ttll1-He mice. Consistently, uptake of PspA by dendritic cells was higher in the nasopharynx-associated lymphoid tissue (NALT) of Ttll1-KO mice than that of Ttll1-He mice. These results indicate that the ciliary function of removing vaccine antigen from the NALT epithelial layer is a critical determinant of the efficacy of nasal vaccine.
Krüppel-Like-Factor 2, a new player in mucosal IgA homeostasis
Authors: Wittner Jens , Schulz Sebastian R , Steinmetz Tobit , Hutloff Andreas R , Cunningham Adam F , Jäck Hans-Martin , Schuh Wolfgang 
Published: January 2023

Abstract
Krüppel-Like-Factor 2 (KLF2) is a transcription factor that controls organ development, differentiation and trafficking of cells. In the immune system, KLF2 fosters the egress of T lymphocytes from the thymus via S1PR1 and promotes quiescent states of B lymphocytes as well as homing of antigen-specific IgG plasmablasts (PB) and plasma cells (PC) to the bone marrow (BM) via the α4β7 receptor.
To investigate the PC-specific role of KLF2, we analyzed CD138+/TACI+ PB/PC subpopulations and isotype changes in various organs such as spleen (SP), BM, gut associated lymphoid tissues (GALT) and blood of KLF2-deficient mice in comparison to their mb1cre+ KLF2wt/wt controls. Therefore, FACS and Elispot analyses showed a striking reduction of IgA+ PB/PC in SP, BM and blood of non-immunized mice. Elisa and multiplex data revealed a strong reduction in serum IgA as well as (s)IgA in the feces of KLF2-deficient mice. However, frequencies of IgA+ PB/PC were not changed in GALT but total PB/PC accumulated in mesenteric lymph nodes (mLN) and Peyer’s Patches. In addition, IgA secretion of these cells was not effected.
Based on these data, we conclude that the observed IgA-deficiency in KLF2-deficient mice can in part be explained by impaired egress of class switched PB/PC from their organ of generation to survival niches in the bone marrow and gut by controlling the expression of integrins.
To address the consequences of a dysregulated PB/PC migration during infection, we are analyzing a GALT-dependent immunization with recombinant Flagellin which is known to trigger a systemic IgG as well as an mucosal IgA response. Furthermore, we are identifying KLF2 target genes that control PC egress and trafficking by RNAseq of IgA+ PB/PC from the mLN of KLF2-deficient mice.
Effect of maternal obesity on neonatal immunity
Authors: Vozenilek Aimee E , Sakai Jiro , Akkoyunlu Mustafa 
Published: January 2023

Abstract

Introduction
Maternal obesity has been shown to enhance infection, autoimmunity, and allergic sensitization in murine offspring. These data suggest that maternal obesity may be altering the neonatal immune system, but this process has not yet been elucidated. In this study, we are investigating the differences between the immune systems of neonatal mice born to obese versus lean mothers. We are also investigating how maternal obesity influences neonatal immune responses to vaccines since most pediatric vaccines are introduced during the first year of life.

Methods
Flow cytometry is used to compare splenocyte populations from neonatal offspring of high-fat and control diet parents. Immune responses of neonates to tetanus toxoid conjugated pneumococcal type 14 polysaccharide vaccines (PPS14-TT) are assessed. RNAseq is performed to investigate differences in peritoneal macrophage inflammatory states in neonatal offspring of high-fat and control-diet parents.

Results
7-day old neonatal mice from high-fat diet parents have a higher percentage of T cells (CD3+) in the spleen compared to neonates from control-diet parents. The high-fat diet offspring also have an increased B cell (B220+) population. Interestingly, although IgG antibody responses to PPS14-TT vaccine was comparable in the neonates from the two groups, those born to obese mothers developed significantly higher levels of IgM antibodies.

Conclusions
Data obtained so far suggest that maternal obesity influences the development of the adaptive immune cell populations and alter the antibody responses to vaccines in neonatal offspring. More detailed analysis of neonatal immune responses to vaccines will be presented at the meeting.
Treg dysfunction in aging oral mucosa
Authors: Pandiyan Pushpa 
Published: January 2023

Abstract
Aging leads to an increased susceptibility to infections, a phenomenon called immunosenescence. An imbalance between proinflammatory and anti-inflammatory mechanisms is also observed during aging. However, mechanisms of mucosal tissue specific infections and inflammation, and the underlying immune cell alterations in these tissues are incompletely understood. Here our objective was to understand oral mucosal immune cells, especially regulatory T cells, a population of CD4+ T cells that are central to immunomodulation. We infected young (2–3 months) and aged (&gt;18–24months) C57BL/6 mice with a sublingual inoculation of 2 × 107 Candida albicans (SC5314) blastospores under anesthesia. We reinfected the mice on day 7 and day 16 after primary infection to mimic recurrent/secondary infections, monitored their weight loss and tongue immunopathology. Control mice were sham infected with PBS. We isolated oral draining cervical lymph nodes (CLN) cells and mouse oral intraepithelial and lamina propria cells (MOIL), and determined the frequency, absolute cell numbers and functions of T and inflammatory CD4 T cells ex vivo before and after infection. We found that aged mice continuously lost weight during the course of the recurrent infections, whereas young mice regained their weight after every infection. Immunosenescent phenotype in aged mice was associated with heightened tongue immunopathology, compared to young mice. Increased oral inflammation phenotype was associated with Treg dysfunctions in local oral tissue. Taken together, our study begins to define T cell dysfunctions and inflammatory processes underlying decline of the immune responses in oral mucosa.