Harvard College

Wyeth

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Michael J Grusby

Mary Collins

Deborah A Young

Matthew James Whitters

Andrea Wurster

Thomas A Wynn

Mark H Kaplan

The present invention provides methods of screening for compositions useful for treating, ameliorating, or preventing fibrosis and/or fibrosis-associated conditions by measuring changes in the level(s) of IL-21 and/or IL-21 receptor (IL-21R) (e.g., the level of expression of IL-21 and/or IL-21R protein and/or mRNA, the level of activity of IL-21 and/or IL-21R, the level of interaction of IL-21 with IL-21R). The invention further provides antagonists of IL-21 or IL-21R for the treatment of fibrosis and/or fibrosis-associated conditions. Further provided herein are methods of diagnosing, prognosing, and monitoring the progress (e.g., the course of treatment) of fibrosis and/or fibrosis-associated conditions by measuring the level of IL-21 and/or IL-21R (i.e., the level of activity of IL-21 and/or IL-21R, the level of expression of IL-21 and/or IL-21R (e.g., the level of IL-21 and/or IL-21R gene products), and/or the level of interaction of IL-21 with IL-21R).

Methods for treating and preventing fibrosis

Methods and compositions for modulating T helper (Th) cell development and function using modulators of IL-21, e.g., human IL-21, activity or level.

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Methods and compositions for modulating T helper (Th) cell development and function

The invention provides methods and compositions for evaluating modulators of the Stat6 signaling pathway; in a particular, transgenic mice comprising a transgene within a Stat6 allele locus, encoding a selectable marker and displacing the SH2-encoding domain of the Stat6 allele. More particularly, the transgene may comprise 3' and 5' regions with sufficient complementarity to the natural Stat6 allele at the locus to effect homologous recombination of the transgene with the Stat6 allele. Such mice provide useful animal models for determining the effect of candidate drugs on a host deficient in Stat6 function. The invention provides a variety of methods for making and using the subject compositions; in particular, methods for determining the effect of a candidate drug on a mouse deficient in Stat6 function and methods of evaluating the side effects of a Stat6 function inhibitor.

Stat6 deficient transgenic mice

Growing community of inventors

Newton, MA, United States of America

Michael J Grusby