Tatyana A Andreyeva

Discovery of an ITK and TRK kinase inhibitor for the potential topical treatment of atopic dermatitis

Jennifer Lynn Duffen, Kimberly K. Crouse, Lin Ji, Amy L. Brault et autres

Interleukin-2-inducible T cell kinase is expressed by T cells and amplifies T cell receptor-dependent signals. Interleukin-2-inducible T cell kinase deletion or inhibition reduces production of interleukin-4 and interleukin-13, key drivers of atopic dermatitis. Nerve growth factor signals via the receptor tropomyosin-related kinase …

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Ligand non-competitive GITR antibody prevents formation of the obligatory signal-triggering GITRL: GITR stoichiometry

Yan Jing, Jessica Haewon Min-DeBartolo, Ching-Shin Huang, M Sharif et autres

The prevalence of autoimmune diseases such as inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) is increasing. Glucocorticoid-induced TNFR-related protein (GITR), a TNF receptor superfamily (TNFRSF) member, is activated by GITR-ligand (GITRL). GITR signaling is pathogenic in models of RA and IBD, …

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A Novel C-C Chemoattractant Cytokine (Chemokine) Receptor 6 (CCR6) Antagonist (PF-07054894) Distinguishes between Homologous Chemokine Receptors, Increases Basal Circulating CCR6+ T Cells, and Ameliorates Interleukin-23-Induced Skin Inflammation

Wěi Li, Kimberly K. Crouse, Jennifer Alley, Richard K. Frisbie et autres

Blocking chemokine receptor C-C chemoattractant cytokine (chemokine) receptor (CCR) 6-dependent T cell migration has therapeutic promise in inflammatory diseases. PF-07054894 is a novel CCR6 antagonist that blocked only CCR6, CCR7, and C-X-C chemoattractant cytokine (chemokine) receptor (CXCR) 2 in a β-arrestin assay …

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Studies with neutralizing antibodies suggest CXCL8-mediated neutrophil activation is independent of C-C motif chemokine receptor-like 2 (CCRL2) ligand binding function

Zhenwei Su, Jonathan Brooks, Jeffrey W. Pelker, Tatyana A Andreyeva et autres

C-C motif chemokine receptor-like 2 (CCRL2) is a non-signaling 7 transmembrane receptor that binds chemotactic ligands to shape leukocyte recruitment to sites of inflammation. However, there is a lack of consensus on the ligands that directly bind CCRL2 or their functional impact. …

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The Interleukin‐1 Receptor–Associated Kinase 4 Inhibitor PF‐06650833 Blocks Inflammation in Preclinical Models of Rheumatic Disease and in Humans Enrolled in a Randomized Clinical Trial

Aaron R. Winkler, Weiyong Sun, Saurav De, Aiping Jiao et autres

OBJECTIVE: To investigate the role of PF-06650833, a highly potent and selective small-molecule inhibitor of interleukin-1-associated kinase 4 (IRAK4), in autoimmune pathophysiology in vitro, in vivo, and in the clinical setting. METHODS: Rheumatoid arthritis (RA) inflammatory pathophysiology was modeled in vitro through …

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Quantitative Analysis of Target Coverage and Germinal Center Response by a CXCL13 Neutralizing Antibody in a T-Dependent Mouse Immunization Model

Joanne Brodfuehrer, Andrew L. Rankin, Jason Edmonds, Sean Keegan et autres

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Selective Inhibition of BTK Prevents Murine Lupus and Antibody-Mediated Glomerulonephritis

Andrew L. Rankin, Nilufer P. Seth, Sean Keegan, Tatyana A Andreyeva et autres

Autoantibody production and immune complex deposition within the kidney promote renal disease in patients with lupus nephritis. Thus, therapeutics that inhibit these pathways may be efficacious in the treatment of systemic lupus erythematosus. Bruton's tyrosine kinase (BTK) is a critical signaling component …

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IL-21R is required for the systemic accumulation of activated B and T lymphocytes in MRL lpr mice (117.9)

Tatyana A Andreyeva, Andrew L. Rankin, Heath Guay, Deborah Herber et autres

Abstract IL-21 is a pleiotropic cytokine that can influence the activation, differentiation and expansion of B and T cells. Lupus prone MRL/MpJ-Fas lpr/lpr /J (MRL lpr ) mice have been shown to develop renal pathology and autoantibodies in an IL-21 dependent manner. …

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IL-21R is critical for the development of memory responses (150.9)

Leslie D Lowe, Andrew L. Rankin, Heather MacLeod, Sean Keegan et autres

Abstract The development of long-term humoral immunity, characterized by the formation of high affinity memory B cells and long-lived plasma cells in the bone marrow, is a major goal of vaccination, but the mechanisms involved in the generation of long-term humoral immunity …

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IL-21 Receptor Is Critical for the Development of Memory B Cell Responses

Andrew L. Rankin, Heather MacLeod, Sean Keegan, Tatyana A Andreyeva et autres

Development of long-term humoral immunity, characterized by the formation of long-lived plasma cells (PCs) in the bone marrow and memory B cells, is a critical component of protective immunity to pathogens, and as such it is the major goal of vaccination. However, …

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In vitro potency, pharmacokinetic profiles and pharmacological activity of optimized anti-IL-21R antibodies in a mouse model of lupus

Yulia Vugmeyster, Heath Guay, Pamela Szklut, Ming Qian et autres

Using phage display, we generated a panel of optimized neutralizing antibodies against the human and mouse receptors for interleukin 21 (IL-21), a cytokine that is implicated in the pathogenesis of many types of autoimmune disease. Two antibodies, Ab-01 and Ab-02, which differed …

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110 Role of IL21R in the pathogenesis of murine models of SLE

Leslie D Lowe, Heath Guay, Tatyana A Andreyeva, Christie Damphousse et autres

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