bluuebunny/crossref_metadata_2025_split huggingface dataset:
UVB induces early increases in IgG+ B cells in lupus-prone but not wild-type mice
Authors: Wolf Sonya , Theros Jonathan , Kahlenberg Michelle 
Published: January 2023

Abstract
At least 45% of patients with systemic lupus erythematousus (SLE) will experience photosensitivity, which is characterized by the development of cutaneous lesions following minimal sun exposure. Clinical and murine evidence support a correlation between ultraviolet (UV) light exposure and induction of systemic lupus flares, including autoantibody production, organ damage mediated by autoantibodies, and immune complex deposition. Therapies for preventing photosensitivity have remained elusive due to an incomplete understanding of the mechanisms involved. This study explores the question of how the B cell population changes after UVB exposure in a lupus prone mouse model (NZM2328) compared to wild-type (Balb/c) mice. In order to examine UVB responses, 10-week old female NZM2328 and Balb/c mice were treated on their dorsal skin with 100mJ/cm2 of UVB for 0,1, 3, or 5 days. No differences in the skin injury process (edema and scaling) were noted between the NZM2328 and Balb/c mice. Notably, however, only the NZM2328 mice showed an increase in the CD19+ IgG+ B cell population in the skin, draining lymph node and spleen within 3days. NZM2328, but not Balb/c mice also exhibited in increase in circulating anti-dsDNA IgG antibodies 2 weeks after 5 days of 100mJ UV treatment. These data suggest that NZM2328 mice have early activation of autoreactive memory B cell populations locally and systemically following UVB exposure compared to wild-type mice. This activation results in increased autoantibodies following UVB treatment. Thus, we propose memory B cell populations as important to photosensitive responses in lupus skin and suggest that targeting memory B cell activation could offer potential as a preventative treatment for SLE flares.
Regulation of Myeloid Derived Suppressor Cell (MDSC) dynamics by T regulatory cells
Authors: Tanwar Shalini , Shevach Ethan M. 
Published: January 2023

Abstract
Multiple sclerosis is an inflammatory demyelinating autoimmune disorder affecting the central nervous system whose severity is reduced using immune suppressive drugs. Therapeutic intervention with interferon-b reduces disease exacerbations and delays relapses. The receptor for type 1 interferon, IFNAR, is present on virtually all cell types making it difficult to dissect the mechanisms involved. We generated mice with a conditional deletion (cKO) of IFNAR in Treg cells (IFNARfl/flFoxp3cre). RNA seq analysis revealed little differences between steady state Treg cells from WT and cKO mice. Yet cKO mice developed severe EAE with an earlier onset than control mice. Although Treg cells from cKO mice appeared to be more activated, the activation status and effector cytokine production of CD4+ and CD8+ T cells in the draining lymph nodes (dLN) was similar in WT and cKO mice during the priming phase, but higher in cKO CD4 T cells in the effector phase. Interestingly, we noted a substantial reduction of myeloid derived suppressor cells (MDSCs) in the dLN of cKO mice, while generation of MDSCs in bone marrow and recruitment to spleen of WT and cKO mice was comparable. CD4+ T cells from cKO mice were found to be defective in chemokine secretion suggesting that IFNAR signaling on Treg cells modulates the capacity of CD4+ T cells to secrete MDSC recruiting chemokines during the priming phase. While modulation of Treg cell number and function by MDSCs has been documented, this study is one of the first to demonstrate that Treg cells may modulate MDSC homing and raises the possibility of a novel role for Treg cells in regulating the kinetics of MDSC recruitment during inflammatory conditions.
Fingolimod impacts innate lymphoid cell biology
Authors: Eken Ahmet , Yetkin Mehmet Fatih , Okus Fatma Zehra , Erdem Serife , Cakir Mustafa , Vural Alperen , Donmez-Altuntas Hamiyet , Mirza Meral , Canatan Halit 
Published: January 2023

Abstract
Group 3 Innate lymphoid cells (ILC3) resemble to Th17 cells in their production of effector cytokines and tissue localization. Th17 cells have been shown to be pathogenic in mouse MS models. Previous studies from others and our lab have shown that Sphingosine 1 phosphate 1 (S1P1) receptor impacts Th17 cell biology. S1P1 receptor agonist Fingolimod is used in the treatment of Multiple sclerosis (MS). To this day, however, the effects of fingolimod on human ILC populations have not been studied. In this study, using PBMCs from Fingolimod-receiving or control relapsing-remitting MS patients, combined with ex vivo culture system we characterized the impact of S1P1 agonists on ILC populations via Flow cytometry, real-time qPCR and ELISA. We report that human ILCs express S1P1 receptor, respond to it, as evident in reduced peripheral ILC cellularity in MS patients receiving Fingolimod. Also in culture, exposure to S1P1 agonists reduced gene expression and secretion of GMCSF and IFN-g by human ILC3 and ILC1, respectively. To our knowledge, this is the first report to study the impact of fingolimod on ILC populations in MS patients.
λ-Carrageenan initiates inflammation via activation of heterodimers TLR2/6 and TLR4/6
Authors: Lewandowski Annie , Deaver Christine M. , Myers Michael J. 
Published: January 2023

Abstract
λ-Carrageenan (λCGN) is frequently used to model local inflammation, however, the mechanism by which λCGN functions has not been fully examined. Swine whole blood was stimulated with λCGN and biomarkers were evaluated. Monocyte Chemotactic Protein-1(MCP-1) and Interleukin-8 protein levels were increased, while Serum Amyloid A (SAA) and Tumor Necrosis Factor-α (TNFα) protein levels were unchanged. Gene expression of MCP-1, Phosphatidylinositol 3-Kinase, and Alveolar Macrophage Chemotactic–II were increased; gene expression of SAA, Interleukin-6, and TNFα were unchanged; and gene expression of Thrombospondin-2 Precursor were decreased. Assessment of which TLRs (Toll-Like Receptors) were involved in the λCGN activation pathway, HEK-293 cells transfected with one plasmid containing either TLR2 or TLR4, along with a second plasmid to release SEAP (secreted embryonic alkaline phosphatase) upon NFκB activation were stimulated with λCGN. TLR2 and TLR4 both showed increased SEAP release after λCGN stimulation. The lack of TNFα production after λCGN stimulation suggested that it was not working through a classic TLR4 homodimer. To determine if a common mechanism could explain these results, RNA silencing studies were initiated. TLR6 was silenced in SEAP HEK-293 cells containing a plasmid for either TLR2 or TLR4. In both cell lines where TLR6 was silenced, λCGN was unable to induce a SEAP response, while these cells maintained responsiveness to a TLR1/2 ligand and a TLR 4 ligand, respectively. These results suggest that λCGN initiates inflammation via TLR2/6 and TLR4/6 heterodimers.
Nitric oxide synthase 2 augments the survival of mice upon Salmonella Typhimurium infection induced sepsis: impact on innate immune responses & organ damage
Authors: Yadav Shikha , Nandi Dipankar 
Published: January 2023

Abstract
Sepsis is defined as infection induced deregulation of host immune responses that may lead to multi organ dysfunction. Enhanced inflammation and persistent organ damage often leads to impaired recovery and death of sepsis patients. Thus molecules that attenuate inflammatory responses are potential therapeutic targets for sepsis. We have established intra-peritoneal S. Typhimurium infection induced peritonitis model of sepsis in mice characterized by: enhanced amounts of nitric oxide (NO), ROS, cytokines, neutrophil recruitment at the site of infection, organ damage and death of mice. Nitric oxide (NO), a highly reactive molecule has pleiotropic effects in host ranging from cell signaling and gene modulation to antimicrobial effects. Enhanced activity of Nos2 and NO is seen in sepsis patients. However, the roles of NO in pathogenesis of sepsis are controversial. Using Nos2−/− mice we attempted to elucidate the roles of Nos2 derived NO in sepsis. Upon infection Nos2−/− mice showed attenuated induction of ROS, pro-inflammatory cytokines and neutrophil recruitment. Importantly, dampened innate immune responses in Nos2−/− mice correlated with increased microbial burden, liver damage, cardiac dysfunction and reduced survival upon sepsis. Clearly Nos2 derived NO promotes protective innate immune responses during sepsis. The precise role of Nos2 derived NO was further evaluated by exogenous supplementation of Nos2−/− mice with a NO donor. Administration of exogenous NO in Nos2−/− mice beneficially restored host innate immune responses and increased survival. Our findings are crucial in the context of therapeutic interventions for sepsis and the implications for NO as a target molecule are discussed.
Macrophage depletion results in anemia, neutrophilia, and is not an effective therapy for rescuing obesity-linked metabolic impairments
Authors: Bader Jackie E. , Enos Reilly T. , Velazquez Kandy T. , Carson Meredith S. , Sougiannis Alexander T. , McGuinness Owen P. , Nagarkatti Mitzi , Nagarkatti Prakash S. , Robinson Cory M. , Fan Daping , Murphy E. Angela 
Published: January 2023

Abstract
Low-grade, chronic inflammation is thought to play a role in obesity-associated metabolic dysfunction. In obesity, macrophages account for approximately 50% of adipose tissue cells and can secrete a variety of proinflammatory cytokines. In this study, we sought to deplete macrophages in order to decrease macrophage-mediated inflammation and rescue metabolic dysfunction. Following 16 weeks of high-fat diet (HFD) (40% of total kcal from fat) or AIN-76A control diet consumption (n=30), male C57BL/6J mice within each diet cohort were assigned to either a clodronate (CLD)-liposome or PBS-liposome-treatment (n=15/group). Mice received 200 μl (1mg) i.p. injections of CLD or PBS-encapsulated liposomes (control group) twice weekly for 4 weeks to deplete macrophages. Metabolic function was assessed via the HOMA-IR, glucose and insulin tolerance tests, and serum free fatty acids. Adipose tissue, liver, and blood were analyzed for macrophage infiltration, inflammatory mediators and circulating cell populations. HFD-fed mice exhibited an obese phenotype compared to the control diet; however, macrophage depletion was unable to rescue metabolic dysfunction. Interestingly, macrophage-depleted mice had &gt;35% increase in circulating neutrophils and adipose tissue Ly6G content. The increase in neutrophils, likely a compensation for the depletion of macrophages, was linked to an increase in the proinflammatory cytokines, IL-6 and IL1β, in the adipose tissue. Additionally, the decrease in macrophages resulted in iron-deficient anemia. Our study suggests that depleting macrophages in an obese setting is not an effective therapy for rescuing metabolic dysfunction and may increase the risk for anemia and adipose tissue inflammation.
Increased salivary levels of Urokinase Plasminogen Activator Receptor (uPAR) are induced by acute stress and correlate with levels of pro-inflammatory cytokines
Authors: Fernandez-Botran Rafael , Szabo Yvette Z. , Lyle Keith B. , Newton Tamara L. 
Published: January 2023

Abstract
Acute and chronic psychological stress are known to trigger components of the inflammatory system resulting in increased levels of pro-inflammatory cytokines (i.e., IL-1β, IL-6 and TNFα). Stress can also result in the activation of the coagulation and fibrinolytic systems via the sympathoadrenal medullary system, resulting in net hypercoagulability. The aim of this study was to investigate the effects of acute stress on the salivary levels of a key component of the fibrinolytic system, urokinase plasminogen activated receptor (uPAR) and determine the relationship with changes in pro- and anti-inflammatory cytokines. Healthy subjects, ages 18–40 (74% female), were randomly assigned to complete a modified Trier Social Stress Test (n = 44) or to recall an angry autobiographical memory (n = 46). Saliva samples, taken at baseline and 60 min post-stress, were used to measure levels of cytokines and uPAR. Acute stress resulted in a significant increase in the salivary levels of uPAR (p&lt;0.0001) when comparing baseline (median [IQR]: 1.83 [2.31] ng/mL) to post-stress samples (2.57 [2.87] ng/mL). The magnitude of the increase in uPAR levels was similar to those for pro- and anti-inflammatory mediators. There were no significant differences between the two types of stressors. There was moderate to moderate-high correlations with the salivary levels of pro-inflammatory, but not anti-inflammatory cytokines, particularly in the post-stressor samples. These results suggest that components of the fibrinolytic system may also influenced by acute stress, prompting further research into understanding their physiological implications. In addition, uPAR levels in saliva may have potential application as stress biomarkers in saliva.
Changes in peritoneal macrophage composition during sepsis.
Authors: Walker Wendy , Rubio Andres , Kumar Devender 
Published: January 2023

Abstract
Sepsis occurs when an infection activates a systemic inflammatory response. The mortality rate for severe sepsis remains high (30–50%). Additionally, many patients who survive sepsis develop a persistent inflammation, immunosuppression and catabolism syndrome (PICS).
Macrophages are early sentinels of infection and exert both beneficial and detrimental functions during sepsis. As phagocytes, they clear pathogens. Macrophages also express pattern recognition receptors, which trigger inflammatory cytokine production. This process plays a key role in host defense; however during sepsis excessive inflammation leads to immune dysregulation and organ dysfunction.
Tissue-resident macrophages include diverse populations with heterogeneous cell surface markers and functions. Two populations exist in the peritoneum of mice: large peritoneal macrophages (LPM; CD11b+, F4/80-hi, MHC-II-lo) and small peritoneal macrophages (SPM; CD11b+, F4/80-lo, MHC-II-hi). These subsets exhibit different levels of phagocytosis and cytokine production.
Importantly, no prior study has comprehensively examined the migration of monocytes, SPM and LPM during sepsis. We used the mouse cecal ligation and puncture model (CLP) to study this process. Our data demonstrate that LPM exit the peritoneum by 18h post-CLP or sham surgery, accompanied by substantial infiltration of monocytes. Within 14 days after sham surgery, LPM have returned to the peritoneum. In contrast, 14 days after CLP there are still few LPM and a large number of monocytes in the peritoneum. These data indicate that, despite an apparent return to homeostasis, an inflammatory process persists in the peritoneum of these mice. This persisting inflammation may contribute to PICS.
Exacerbation of intestinal IL-17 activity by mycoplasma superantigen leads to increased HMGB1 and chemokines in the joints of autoimmune arthritis mice
Authors: Mu Hong-Hua , Tran Justin 
Published: January 2023

Abstract
An infection can amplify an autoimmune disease by either exacerbating an ongoing disorder, including a relapse, or by leading to chronic progressive disease. We have been studying a mouse autoimmune arthritis model by infecting mice with the Mycoplasma arthriditis. M. arthritidis produces a potent superantigen (SAg) MAM, which is known to be responsible for the autoimmune arthritis induced in susceptible mouse strains. Because the mechanisms leading from systemic autoimmunity to joint-specific autoimmune disease are still unclear, we questioned if autoimmunity initiates at mucosal sites, i.e., gut and lung. In the present study, mice were systemically immunized with collagen II and MAM superantigen, a week later, IL-17 and HMGB1 (the high mobility group box 1, a stress protein) were highly represented within intestinal lamina propria. Levels of IL-17 and HMGB1 in the gut were closely related to the severity of arthritis. The infiltration of inflammatory leukocytes in the joints were found 3 to 5 weeks after IL-17/HMGB1 were seen in the gut. We also showed that IL-17/HMGB1 synergetically stimulate synoviocytes to release a spectrum of chemokines, CXCL1, CXCL2, CXCL12, CCL2 and CCL5, and attracted inflammatory leukocytes. In vivo blocking of IL-17 and/or HMGB1 greatly reduced arthritis severity and joint destruction. Our results suggests that, the synergetic effect of IL-17 and HMGB1 which initiate autoimmunity in the gut is critical for bridging the inflammatory signals between the gut and the joints, and promoting the infiltration of inflammatory cells in the joints. Thus we might develop a therapeutic strategy to reduce inflammatory response and joint destruction by targeting IL-17 and HMGB1 at mucosal sites in autoimmune arthritis.
Pre-existing atopy protects mice from paramyxoviral respiratory infection weight loss
Authors: Hussain Syed-Rehan A. , Rohlfing Michelle , Santoro Jennifer , Grayson Mitchell H. 
Published: January 2023

Abstract
Severe paramyxoviral infections early in life have been associated with development of asthma and allergies; respiratory viral infections are known to exacerbate asthma. We have a mouse model of a severe paramyxviral respiratory infection using murine parainfluenza virus 1, Sendai virus (SeV). C57BL6 mice inoculated with SeV develop a severe acute infection demonstrated by significant weight loss over 8–10 days. The mice recover and are left with long-lasting airway hyper-reactivity and mucous cell metaplasia. Exposure to a non-viral antigen during the acute infection leads to IgE production against the non-viral antigen (allergic sensitization). While this model provides an explanation for development of allergies and asthma, it is not known whether being atopic before viral infection alters the disease state. To address this, we intranasally sensitized and challenged C57BL6 mice with house dust mite extract (HDM) or PBS, and one week later inoculated the mice with 2×105 pfu SeV or ultraviolet light inactivated SeV (UV-SeV). All UV-SeV groups lost no weight. SeV infection in PBS sensitized/challenged (PBS/PBS/SeV) mice led to a 10.8+/−2.5% weight loss from baseline (mean+/−SEM, n=4); surprisingly, HDM sensitized and challenged mice lost no weight with SeV infection (−1.7+/−0.6% weight loss, n=4, p=0.0022 versus PBS/PBS/SeV). Mice HDM sensitized but not challenged loss 10.8+/−1.6% weight with SeV infection (n=4, p&gt;0.99 versus PBS/PBS/SeV). Whether the weight loss protection from HDM sensitization/challenge alters the antiviral immune response and/or protects against post-viral atopic disease is being investigated. These data suggest atopy may protect against symptoms of a severe paramyxoviral respiratory infection.
Principal Component Analysis to Evaluate Relationships in Reactivity to Commercial Extracts and Uncharacterized Fungi among Asthmatic and Allergic Rhinitis Subjects
Authors: Rivera-Mariani Felix Emanuel , Bolaños-Rosero Benjamín 
Published: January 2023

Abstract

Rationale
Identifying patterns in reactivity to allergens can uncover shared respiratory health risks among subjects suffering from chronic respiratory diseases. Therefore, there is a need to identify statistical approaches that can expose inter-allergen relationships.

Methods
: We implemented spearman, exponential, and logistic principal component analysis on specific immunoglobulin-E (sIgE) levels, reactivity to commercial extracts, basidiomycetes (Ganoderma sp, Chlorophyllum sp, Pleurotus sp) crude extracts, and to previously uncharacterized fungal airborne particulate among asthmatics, allergic and non-allergic rhinitis subjects.

Results
: Positive correlations (p = 0.03 to p &lt; 0.001) were identified between reactivity of two commercial fungal extracts (Aspergillus sp, Alternaria sp), and among all three basidiomycete crude extracts (Ganoderma sp., Chlorophyllum, sp, Pleurotus sp.; p = 0.01 to p &lt; 0.001). sIgE levels correlated with all five categories of airborne fungal particulates (un-identified particulates, ascospores, basidiospores, fungal fragments, and mitosporic fungi), but only with three extracts (Aspergillus sp., Alternaria sp, and Chlorophyllum sp). Based on reactivity to fungal airborne particulate, we identified three groups: subjects reactive to ascospores, reactive to basidiospores and unidentified particulate, and reactive to mitosporic fungi and fungal fragments.

Conclusions
: Our finding suggests that PCA of sIgE, together with reactivity to commercial and previously uncharacterized allergens present a suitable strategy to identify respiratory health risks among individuals suffering from chronic respiratory diseases, such as asthma and allergic rhinitis.
A potential role for adipose tissue eosinophils in allergy and asthma.
Authors: Bolus William Reid , Hasty Alyssa 
Published: January 2023

Abstract
Allergy can take many forms, but a mutual trait is the hypersensitive immune response to what the body detects as foreign. A common form of airway allergy is asthma, which affects &gt;235 million people worldwide and is the most common chronic disease among children. Interestingly, obese individuals have a staggering 92% increased risk of asthma, displaying enhanced asthmatic symptoms, airway hyper-responsiveness, & atopy. Due to the clinical correlation between obesity & asthma, scientific endeavors have sought to explain the causality. Studies have shown adipokines secreted from adipose tissue (AT) can have either pro- or anti-inflammatory effects on the lungs. Furthermore, diet-induced obesity increases migration of eosinophils from bone marrow to the lung, as well as delays exit from the airway epithelium to the lumen. Curiously, investigators have tried to understand the correlative link between asthma & obesity without closely examining the AT itself. Our data shows for the first time that AT mounts a hypereosinophilic state upon repeated exposure to a foreign substance (i.e. a hallmark of allergy & asthma in lung); increasing eosinophils from ~5% to 60% of AT leukocytes in obese mice. A single exposure does not elicit an eosinophilic response, potentially suggesting a role for the adaptive immune system. We found that obesity increased sensitivity of this immune response. Furthermore, the surge in AT eosinophils was dependent on IL33, a required cytokine for eosinophilic accumulation in lung during allergy. We are determining if other classic indicators of allergy are present in AT of our model. Ultimately, we hope to elucidate whether AT & lung act within a feedback loop that contributes to the incidence/severity of allergy & asthma.