Methods for the treatment and prevention of inflammatory diseases

Abstract

The inventors demonstrate that treatment of young, suckling mice with a glycolipid derived from Helicobacter pylori activates NKT cells in a CD1d-restricted fashion, and is protective against AHR in a model of allergen-induced asthma. The inventors further found that this protective effect can be transferred by NKT cells exposed to the glycolipid, and is associated with the expansion of a suppressive double-negative NKT cells and Foxp3+ TReg cells. The inventors also demonstrate herein that pretreatment of adult mice with a glycolipid derived from Helicobacter pylori partially suppresses airway hyperreactivity and inhibits BAL inflammation in an ozone-exposure model. Accordingly, provided herein are compositions and methods for the treatment and prevention of inflammatory diseases, such as asthma or autoimmune diseases, in a subject in need thereof.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims benefit under 35 U.S.C. § 119(e) of U.S. Provisional Patent Application Ser. No. 61 / 421,797 filed on Dec. 10, 2010 and U.S. Provisional Patent Application Ser. No. 61 / 347,596 filed on May 24, 2010, the contents of each of which are incorporated herein in their entireties by reference.GOVERNMENT SUPPORT[0002]The invention was made with Government support under grants R01 AI68085, R01 HL62348, R01 AI026322, and RC1HL069507 awarded by the National Institutes of Health (NIH). The Government has certain rights in the invention.FIELD OF THE INVENTION[0003]The present invention relates to methods and glycolipid compounds for the treatment of inflammatory disease, such as asthma and autoimmune diseases.BACKGROUND OF THE INVENTION[0004]Bronchial asthma, a complex and heterogeneous trait, is a major public health problem, affecting nearly 10% of the general population, and disproportionately affecting children. Moreover, the...

AI Technical Summary

Benefits of technology

[0008]As described herein, the inventors demonstrate that immunological exposure to viruses and bacteria at a young age can provide protection against the later initiation of allergic asthma, and that this protective effect can be transferred via NKT cells. The inventors demonstrate that treatment of young, suckling mice with a glycolipid derived from Helicobacter pylori (a bacterium associated with protection against asthma), activates NKT cells in a CD1d-restricted fashion, and is protective against AHR in a model of allergen-induced asthma. The inventors further found that this protective effect can be transferred by NKT cells exposed to the glycolipid, and is associated with the expansion of a suppressive double-negative NKT cells and Foxp3+ TReg cells. The inventors also demonstrate herein that pre-treatment of adult mice with the glycolipid derived from Helicobacter pylori partially suppresses airway hyperreactivity and inhibits BAL inflammation in an ozone-exposure model. The inventors further demonstrate that young, suckling mice infected with influenza A are protected as adults against allergen-induced airway hyperreactivity (AHR). The protective effect was associated with the preferential expansion of CD4−CD8−, but not CD4+, natural killer T (NKT) cells, and required T-bet and TLR7. Adoptive transfer of this population into allergen-sensitized adult mice suppressed the development of allergen-induced AHR, while expanding allergen-specific Foxp3+ TReg cells. The findings discovered by the inventors provide novel regulatory pathways, and new therapeutic strategies for the prevention and treatment of inflammatory diseases requiring immune regulation and suppression, such as asthma and autoimmune diseases.

Problems solved by technology

Bronchial asthma, a complex and heterogeneous trait, is a major public health problem, affecting nearly 10% of the general population, and disproportionately affecting children.

The role of viral infection in modulating the development of asthma is particularly complex, because many different viruses affect the respiratory tract, some appearing to enhance and some appearing to protect against the development of asthma.

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