RIP2: a mediator of signaling in the innate and adaptive immune systems
OwnerRichard A. Flavell, Ruslan M. Medzhitov +1inventors
InventorsRichard A. Flavell, Ruslan M. Medzhitov, Koichi Kobayashi
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Abstract
This invention provides a method of identifying a compound that modulates an innate immune response and an adaptive immune response comprising contacting cells expressing RIP2 with a candidate compound, and determining whether the candidate compound modulates RIP2 activity in the cells, wherein modulation of RIP2 activity in the cells by the candidate compound indicates that the candidate compound modulates the innate immune response and adaptive immune response.
Claims52
A method of identifying a compound that modulates an innate immune response and an adaptive immune response comprising contacting cells expressing RIP2 with a candidate compound, and determining whether the candidate compound modulates RIP2 activity in the cells, wherein modulation of RIP2 activity in the cells by the candidate compound indicates that the candidate compound modulates the innate immune response and the adaptive immune response.
A method of identifying a compound that produces an anti-inflammatory effect and an immuno-inhibitory effect comprising contacting cells expressing RIP2 with a candidate compound and determining whether the candidate compound inhibits RIP2 activity in the cells, wherein if inhibition of RIP2 activity by the candidate compound occurs compound that produces an anti-inflammatory effect and an immuno-inhibitory effect is identified.
A method of determining whether a compound is a RIP2 inhibitor comprising comparing a cell's RIP2 activity both in the presence and absence of the candidate compound, wherein a decreased activity of RIP2 in the presence of the compound indicates that the compound is a RIP2 inhibitor.
A method of producing an anti-inflammatory effect and an immuno-inhibitory effect in an individual, comprising administering to the individual a compound that inhibits RIP2 in sufficient quantity to inhibit RIP2, thereby producing an anti-inflammatory effect and an immuno-inhibitory effect in the individual.
A method of treating an inflammatory condition in an individual comprising administering to the individual a compound that inhibits RIP2 activity in the individual, thereby producing an anti-inflammatory effect in the individual.
Use of a compound which inhibits RIP2 for the preparation of a medicament which provides an anti-inflammatory effect and immuno-inhibitory effect in an individual.
Use of a compound which inhibits RIP2 for the preparation of a medicament for treating an inflammatory condition in an individual.
A method of determining whether a compound is a RIP2 inhibitor comprising:
- a. contacting a cell expressing RIP2 with a candidate compound and measuring the cell's production of an inflammatory cytokine or chemokine upon stimulation with a TLR ligand;
- b. comparing the cell's production of the inflammatory cytokine or chemokine in step (a) with the cell's production of the inflammatory cytokine or chemokine in the absence of the candidate compound;
- c. contacting a cell which does not express RIP2 with the candidate compound and measuring the cell's production of an inflammatory cytokine or chemokine upon stimulation with a TLR ligand;
- and
- d. comparing the cell's production of the inflammatory cytokine or chemokine in step (c) with the cell's production of the inflammatory cytokine or chemokine in the absence of the candidate compound;
- wherein the production measured in (a) is less than the production measured in (b), and the production measured in step (c) is comparable to the production measured in step (d) indicates that the compound is a RIP2 inhibitor.
A method of determining whether a compound is a RIP2 inhibitor comprising:
- a. contacting a cell expressing RIP2 with a candidate compound and measuring the cell's production of an inflammatory cytokine or chemokine upon stimulation with a pathogen;
- b. comparing the cell's production of the inflammatory cytokine or chemokine of step (a) with the cell's production of the inflammatory cytokine or chemokine in the absence of the candidate compound;
- c. contacting a cell which does not express RIP2 with the candidate compound and measuring the cell's production of an inflammatory cytokine or chemokine upon stimulation with a pathogen;
- and
- d. comparing the cell's production of the inflammatory cytokine or chemokine in step (c) with the cell's production of the inflammatory cytokine or chemokine in the absence of the candidate compound;
- wherein the production measured in (a) is less than the production measured in (b), and the production measured in step (c) is comparable to the production measured in step (d) indicates that the compound is a RIP2 inhibitor.
A method of determining whether a compound is a RIP2 inhibitor comprising:
- a. contacting a cell expressing RIP2 with a candidate compound and measuring NF-κB activation in the cell;
- b. comparing the NF-κB activation measured in step (a) with the activation of NF-κB measured in a cell expressing RIP2 in the absence of the candidate compound;
- c. contacting a cell which does not express RIP2 with the candidate compound and measuring the activation of NF-κB in the cell;
- and
- d. comparing the NF-κB activation measured in step (c) with the NF-κB activation measured in a cell which does not express RIP2 in the absence of the candidate compound;
- wherein the activator measured in (a) is less than the activation measured in (b), and the activation measured in step (c) is comparable to the activation measured in step (d) indicates that the compound is a RIP2 inhibitor.
A method of determining whether a compound is a RIP2 inhibitor comprising:
- a. contacting a cell expressing RIP2 with a candidate compound and measuring cell proliferation, upon stimulation with IL-2 or Concanavalin A, alone or together with IL-1β;
- b. comparing the cell proliferation in step (a) with the proliferation of a cell expressing RIP2 in the absence of the candidate compound, upon stimulation with IL-2 or Concanavalin A, alone or together with IL-1β.
- c. contacting a cell which does not express RIP2 with the candidate compound and measuring cell proliferation, upon stimulation with IL2 or Concanavalin A, alone or together with IL-1β;
- and
- d. comparing the cell proliferation in step (c) with the proliferation of a cell which does not express RIP2 in the absence of the candidate compound upon stimulation with IL-2 or Concanavalin A, alone or in combination with IL-1β;
- wherein cell proliferation measured in step (a) is less than in step (b), and cell proliferation in step (c) is comparable to step (d) indicates that the compound is a RIP2 inhibitor.
A method of determining whether a compound is a RIP2 inhibitor comprising:
- a. contacting a cell expressing RIP2 with a candidate compound and measuring the amount of the cell's IL-2 production upon T cell receptor stimulation;
- b. comparing the amount of IL-2 measured in step (a) with an amount of the cell's IL-2 production in the absence of the candidate compound upon T cell receptor stimulation;
- c. contacting a cell which does not express RIP2 with the candidate compound and measuring the cell's IL-2 production upon T cell receptor stimulation;
- and
- d. comparing the amount of IL-2 measured in step (c) with an amount of IL-2 produced by a cell that does not express RIP2 in the absence of the candidate compound upon T cell receptor stimulation;
- wherein an amount measured in step (a) is less than step (b), and an amount measured in step (c) is comparable to the amount measured in step (d) indicates that the compound is a RIP2 inhibitor.
A method of determining whether a compound is a RIP2 inhibitor comprising:
- a. contacting cells expressing RIP2 with a candidate compound and measuring proliferation of the cells upon T cell receptor stimulation;
- b. comparing the amount of proliferation measured in step (a) with the proliferation of cells expressing RIP2 in the absence of the candidate compound upon T cell receptor stimulation;
- c. contacting cells which do not express RIP2 with the candidate compound and measuring the proliferation of the cells upon T cell receptor stimulation;
- d. comparing the amount of proliferation measured in step (c) with the proliferation of cells which do not express RIP2 in the absence of the candidate compound upon T cell receptor stimulation;
- wherein an amount measured in step (a) is less than step (b), and an amount measured in step (c) is comparable to the amount measured in step (d) indicates that the compound is a RIP2 inhibitor.
An isolated cell which does not express RIP2.
An isolated cell which does not normally express RIP2, which comprises an exogeneous nucleic acid encoding RIP2.
Dependencies are inferred from the claim text.