Modulating immune system development and function through microrna mir-146

Abstract

The present disclosure relates to the finding that microRNA-146 plays a role in modulating the development and function of the immune system. Immune cell development and function can be modulated by delivery of microRNA-146 (miR-146) or antisense miR-146 to target immune cells or precursor cells. For example, in some embodiments, activity and / or proliferation of certain immune cells is regulated by administering miR-146 oligonucleotides or anti-miR-146 oligonucleotides. In other embodiments, pro-inflammatory cytokine expression in immune cells is regulated by administering a miR-146 oligonucleotide or anti-miR-146. In further embodiments, methods of regulating macrophage activity using antisense miR-146 are provided. Additional methods and compositions for regulating immune system function and development using miR-146 are disclosed.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]The present application claims priority under 35 U.S.C. §120 as a continuation of U.S. patent application Ser. No. 12 / 337,525, filed Dec. 17, 2008, which claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application No. 61 / 007,987, filed on Dec. 17, 2007. All of the aforementioned priority applications are herein expressly incorporated by reference in their entirety.STATEMENT REGARDING FEDERALLY SPONSORED R&D[0002]The U.S. Government has certain rights in this invention pursuant to Grant No. GM039458 awarded by National Institutes of Health.REFERENCE TO SEQUENCE LISTING[0003]The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled CALTE.045C1.TXT, created Jun. 1, 2011, which is 5.2 KB in size. The information in the electronic format of the Sequence Listing is incorporated herein by reference in its entirety.BACKGROUND OF THE INVENTION[0004]1. ...

AI Technical Summary

Benefits of technology

[0017]In some embodiments methods of increasing proliferation and / or activity of immune cells, such as B1 B cells, Marginal Zone B cells and Natural Killer cells and CD8+ T cells, are provided. In some embodiments, the methods comprise administering a miRNA-146 oligonucleotide to a target cell or target tissue, such as bone marrow. In other embodiments, the methods comprise administering a miRNA-146 expression vector to target cells or a target tissue and expressing a miRNA-146 in the target. In some embodiments, total numbers of one or more of B1 B cells, Marginal Zone B cells and Natural Killer cells and CD8+ T cells can be increased in a host by these methods.

[0018]In other embodiments, methods of decreasing proliferation and / or activity of immune cells such as B1 B cells, Marginal Zone B cells and Natural Killer cells and CD8+ T cells are provided. In some embodiments, the methods comprise administering antisense miRNA-146 oligonucleotides to target cells or a target tissue, such as bone marrow. In other embodiments, the methods comprise administering an antisense miRNA-146 expression vector to target cells or a target tissue such that antisense miRNA-146 is expressed in the target. In some embodiments, total numbers of one or more of B1 B cells, Marginal Zone B cells and Natural Killer cells and CD8+ T cells can be decreased in a host by these methods.

[0019]In other embodiments, proliferation and / or activity of immune cells such as B2 B cells and CD8αα+ T cells can be upregulated. In some embodiments, the methods comprise administering an antisense miRNA-146 oligonucleotide to target cells or a target tissue, such as bone marrow. In other embodiments, the methods comprise administering an antisense miRNA-146 expression vector to a target tissue such that antisense miRNA-146 is expressed in the target tissue. In some embodiments, total numbers of B2 B cells and / or CD8αα+ T cells can be increased in a host by these methods.

Problems solved by technology

Inflammation is a highly complex defense reaction of the host in response to an invading pathogen or injury, which when not resolved swiftly can result in quite severe pathological consequences.

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