Leading the way to a cure

Lupus Research Update: 2007 Volume 1

Volume 1, 2007 - Online Edition | In This Issue

The results are in! >
ALR's 2007 grant recipients >
One Love. One Cause. ALR Gala a Smashing Success >
The Faces of Lupus >
Advocacy Update — ALR Goes to Washington >
Research Results - Rituximab Results in Long-Term Immune Alteration in Some Lupus Patients >
Research Results — Exploring Toll-Like Receptors’ (TLR) Role in Lupus >
Research Results – The Role of Myeloid Dendritic Cells in Lupus >
News Flash – American College of Rheumatology Annual Meeting Update >
FDA Warning on Rituximab >
Drug Research and Development News >
Beyond the Research - 2007 Walk Sites Announced >

Research Results – Exploring Toll-Like Receptors’ (TLR) Role in Lupus

Toll-like receptors, or TLRs, are proteins that help cells recognize foreign substances. They’re part of our innate immune system, enabling us to respond quickly to infectious agents. In the past few years, researchers have found that TLRs play some role in the ability of B cells’ to recognize autoantigens, particularly those that contain nucleic acids like DNA. (You can read more on TLRs on page 6).

A study by ALR-funded researchers Philip L. Cohen, M.D., and Robert A. Eisenberg, M.D., and their colleagues at the University of Pennsylvania focused on TLR9 in a lupus-like mouse model called the chronic graft-vs-host model. The researchers reported in the Nov. 15, 2006 issue of the Journal of Immunology that they found varying effects of TLR9 on autoimmunity. In some cases, mice without the protein had less severe lupus-like disease with lower autoantibody levels; in other cases, the presence of the protein made no difference; and in some cases, it seemed to enhance production of autoantibodies.

“It’s likely that TLR9 plays a role in both the induction and breaking of tolerance to DNA, depending on the circumstances,” says Dr. Eisenberg. Overall, he said, his group’s findings, as well as findings by other researchers investigating TLRs in different mouse models, suggest that targeting this protein may provide a potential therapy. “But it remains to be seen just how it would be done, and there is a potential to make things worse,” he says.

Ma Z, J Chen F, Madaio MP, Cohen PL Eisenberg RA. Modulation of autoimmunity by TLR9 in the chronic graft-vs-host model of systemic lupus erythematosus. J Immunol. 2006 Nov 15;177(10):7444-50.

Just the Facts

What the studies showed: TLR9 plays a role in lupus as seen in the chronic graft-vs-host mouse model. What it means: New treatments for lupus could target TLR9 and other TLRs in some way, but they will need to be developed with caution.

What’s next: Other groups are investigating TLRs in more detail, trying to learn where, when and how they act.

ALR funding: Philip L. Cohen: $500,000, Robert L. Eisenberg: $500,000



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