A5100450931- Immune Response and Inflammation
- Adipose Tissue and Metabolism
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- NF-κB Signaling Pathways
- Asthma and respiratory diseases
- Cultural Heritage Management and Preservation
- Diet and metabolism studies
- Kruppel-like factors research
- Liver Disease Diagnosis and Treatment
- Nutrition and Health in Aging
- Psoriasis: Treatment and Pathogenesis
- interferon and immune responses
- Fibroblast Growth Factor Research
- Parasite Biology and Host Interactions
- Systemic Lupus Erythematosus Research
- GDF15 and Related Biomarkers
- Immune cells in cancer
- Tryptophan and brain disorders
- Mast cells and histamine
- Dietary Effects on Health
- Adipokines, Inflammation, and Metabolic Diseases
- Genetic Syndromes and Imprinting
- Ancient Mediterranean Archaeology and History
- Immunotherapy and Immune Responses
Yale University
2016-2025
Tianjin Medical University General Hospital
2025
University of California, San Diego
2017-2025
Dell Children's Medical Center of Central Texas
2025
Monash Health
2025
Western University
2025
The University of Texas Southwestern Medical Center
2006-2024
Qinghai University
2024
University of New Haven
2023
University of Chicago
2019-2023
The y-linked autoimmune accelerating (yaa) locus is a potent disease allele. Transcription profiling of yaa-bearing B cells revealed the overexpression cluster X-linked genes that included Tlr7. FISH analysis demonstrated translocation this segment onto yaa chromosome. resulting Tlr7 increased in vitro responses to Toll-like receptor (TLR) 7 signaling all males. B6.yaa mice are not overtly autoimmune, but addition Sle1, which contains autoimmune-predisposing Slam/Cd2 haplotype, causes...
The intestine is a site of direct encounter with the external environment and must consequently balance barrier defense nutrient uptake. To investigate how uptake regulated in small intestine, we tested effect diets different macronutrient compositions on epithelial gene expression. We found that enzymes transporters required for carbohydrate digestion absorption were by availability. "on-demand" induction this machinery γδ T cells, which program through suppression interleukin-22 production...
Abstract In addition to its canonical function of protection from pathogens, the immune system can also alter behaviour 1,2 . The scope and mechanisms behavioural modifications by are not yet well understood. Here, using mouse models food allergy, we show that allergic sensitization drives antigen-specific avoidance behaviour. Allergen ingestion activates brain areas involved in response aversive stimuli, including nucleus tractus solitarius, parabrachial central amygdala. requires...
The Y-linked autoimmune accelerating (Yaa) locus drives the transition to fatal lupus nephritis when combined with B6.Sle1 in our C57BL/6J (B6)-congenic model of systemic autoimmunity. We and others recently demonstrated that translocation a cluster X-linked genes onto Y chromosome is genetic lesion underlying Yaa (Subramanian, S. et al., Proc. Natl. Acad. Sci. USA 2006. 103: 9970-9975; Pisitkun, P. Science 312: 1669-1672). In male mice carrying Yaa, transcription several within translocated...
Our current understanding of immunity to pathogens suggests that anatomic coupling antigens with danger signals is a required feature for the formation immune memory. However, in context pathogen-independent inflammation, stringency this anatomical unclear. Here, we demonstrate multiple modes skin injury were sufficient induce humoral response introduced gut. Skin damage induced narrow subset endocrine cytokines necessary and priming at various distal tissues. Thus, addition “local priming”...
<h3>Background:</h3> Intestinal allograft rejection resembles Crohn’s disease clinically and pathologically. An understanding of its mechanism could impact this life-saving procedure, as well provide insight into the pathophysiology inflammatory bowel disease. The NOD2 protein has been implicated a key player in intestinal immune health, consequence discovery three polymorphisms linked with investigation was carried out to determine whether epithelial function graft survival were influenced...
Among various surface molecules screened, CXCR4 was significantly up-regulated on monocytes, neutrophils, B cell subsets, and plasma cells in multiple murine models of lupus with active nephritis, including B6.Sle1Yaa, BXSB, MRL.lpr. TLR-mediated signaling inflammatory cytokines accounted part for this increase. Increased expression associated functional consequences, increased migration enhanced survival. Simultaneously, the ligand CXCR4, CXCL12, nephritic kidneys. Treatment a peptide...
Abstract Objective CXCR4 is a chemokine with multiple effects on the immune system. In murine lupus models, we demonstrated that monocytes, neutrophils, and B cells overexpressed its ligand, CXCL12, was up‐regulated in diseased kidneys. We undertook this study to determine whether expression increased peripheral blood leukocytes from patients systemic erythematosus (SLE) CXCL12 kidneys SLE. Methods Peripheral 31 SLE patients, 8 normal controls, 9 rheumatoid arthritis were prospectively...
Apremilast, an oral phosphodiesterase 4 inhibitor, demonstrated effectiveness (versus placebo) for treatment of active psoriatic arthritis in the long-term assessment clinical efficacy (PALACE) phase III trial program. Pharmacodynamic effects apremilast on plasma biomarkers associated with inflammation were evaluated a PALACE 1 substudy. Of 504 patients randomized 1, 150 (placebo:<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"...
Significance Feeding behavior changes drastically with infection and is a conserved behavioral response. However, the mechanistic aspects of how this provides survival advantage are poorly understood. Metabolic reprogramming emerging as mechanism by which disease tolerance established coordinated to type inflammatory insult support tissue function. The metabolism required for parasitic infections has not yet been explored. Here, we report that inhibition glycolysis utilizing 2-deoxy glucose...
Secondary hemophagocytic lymphohistiocytosis (sHLH) is a highly mortal complication associated with sepsis. In adults, it often seen in the setting of infections, especially viral but mechanisms that underlie pathogenesis are unknown. sHLH characterized by hyperinflammatory state and presence hemophagocytosis. We found sequential challenging mice nonlethal dose toll-like receptor (TLR) agonist followed TLR4 agonist, not other permutations, produced lethal recapitulates many aspects human...
Increasing age is the strongest predictor of risk COVID-19 severity and mortality. Immunometabolic switch from glycolysis to ketolysis protects against inflammatory damage influenza infection in adults. To investigate how compromises defense coronavirus infection, whether a pro-longevity ketogenic diet (KD) impacts immune surveillance, we developed an aging model natural murine beta (mCoV) with mouse hepatitis virus strain-A59 (MHV-A59). When inoculated intranasally, mCoV pneumotropic...
Cells found within atherosclerotic lesions can produce in culture protein mediators that may participate atherogenesis. To test whether human atheromata actually contain transcripts for certain of these genes, we compared levels mRNAs carotid or coronary and nonatherosclerotic vessels by polymerase chain reaction (PCR) amplification cDNAs reverse-transcribed from RNA. We measured PCR products (generated during exponential amplification) incorporation 32P-labeled primers. Levels interleukin 1...
Palmoplantar psoriasis is a variant of resistant to many forms treatment.Twenty subjects with moderate-to-severe the palms and soles, 50% pustules at baseline, were treated ustekinumab weeks 0, 4, 16. All had previously failed topical corticosteroids. Dosing was 45 mg subcutaneously for weighing <100 kg 90 ≥100 kg. The primary endpoint percent achieving clinical clearance week 16, defined as Palm-Sole Physician's Global Assessment ≤1. study received Tufts Medical Center IRB approval.After 16...
Mutations of the CBP/p300 histone acetyltransferase (HAT) domain can be linked to leukemic transformation in humans, suggestive a checkpoint leukocyte compartment sizes. Here, we examined impact reversible inhibition this by small-molecule A485. We found that A485 triggered acute and transient mobilization leukocytes from bone marrow into blood. Leukocyte was equally potent as, but mechanistically distinct from, granulocyte colony-stimulating factor (G-CSF), which allowed for additive...
Meal ingestion increases body temperature in multiple species, an effect that is blunted by obesity. However, the mechanisms responsible for these phenomena remain incompletely understood. Here we show refeeding plasma leptin concentrations approximately 8-fold 48-hour-fasted lean rats, and this normalization of stimulates adrenomedullary catecholamine secretion. Increased adrenal medulla-derived catecholamines were necessary sufficient to increase postprandially, a process required both...
Stimulation of the innate immune system is crucial in both effective vaccinations and immunotherapies. This often achieved through adjuvants, molecules that usually activate pattern recognition receptors (PRRs) stimulate two signaling pathways: nuclear factor kappa-light-chain-enhancer activated B-cells pathway (NF-κB) interferon regulatory factors (IRF). Here, we demonstrate ability to alter improve adjuvant activity via addition small molecule "immunomodulators". By modulating instead...