Methods for screening for modulators of CXCR3 signaling
AssigneeUniversity of Maryland, Baltimore
InventorsAlessio Fasano, Ruiliang Lu, Stefanie N. Vogel, Julie Brownley, Karen Lammers
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Abstract
CXCR3 is identified as a physiological receptor for Gliadin. Assays for determining modulators of CXCR3 signaling are provided. Fragments of gliadin which function as inhibitors of CXCR3 signaling can be determined. Methods for treating diseases relating to gluten and/or autoimmunity by targeting CXCR3 are provided. Such diseases include celiac disease, gluten sensitivity, gluten allergy, rheumatoid arthritis, multiple sclerosis, immune-mediated or type 1 diabetes mellitus, inflammatory bowel diseases, systemic lupus erythematosus, psoriasis, scleroderma, and autoimmune thyroid diseases.
Claims17
A method for identifying a gliadin, or fragment of gliadin, which binds the Chemokine (C-X-C motif) receptor 3, comprising:
- contacting a gliadin, or fragment of gliadin, comprising at least six amino acid residues with a Chemokine (C-X-C) motif receptor 3;
- and
- determining binding of the gliadin or fragment of gliadin to the Chemokine (C-X-C motif) receptor 3 using fluorescence activated cell sorting, fluorescent microscopy, fluorescent spectrophotometry, 2-hybrid transactivation, fluorescent polarization, nuclear magnetic resonance, fluorescent energy transfer or transcriptional activation.
A method for identifying a gliadin, or fragment of gliadin, which modulates a Chemokine (C-X-C motif) receptor 3 cell signaling event, comprising:
- contacting a gliadin, or fragment of gliadin comprising at least six amino acid residues, with a first cell which expresses Chemokine (C-X-C motif) receptor 3 and with a second cell which does not express Chemokine (C-X-C motif) receptor 3;
- and
- comparing the amount of the cell signaling event between the two cell types using a trans epithelial electrical resistance assay, a zonulin release assay, a microglia recruitment assay, a tyrosine kinase phosphorylation assay, a trysosine kinase chemotaxis assay, a MMP-2 gelatinolytic activity assay, or a MMP-9 gelatinolytic activity assay.
Dependencies are inferred from the claim text.