Press releases
Please quote Nature Immunology as the source of these items.
The May 2007 issue of Nature Immunology is available online.
May 2007
Autoantibody production by perturbed B cells
Chronic low-level expression of a molecule called 'thymic stromal lymphopoietin' (TSLP) can greatly alter the development of antibody-producing B cells, according to a paper published online this week in Nature Immunology.
David Rawlings and colleagues show that low amounts of TSLP produced by epithelial tissues in skin and lung can accelerate the premature release of B cells from the bone marrow, bypassing normal mechanisms that ensure these cells do not attack �self� tissues. Additionally, TSLP triggers an increase in a particular subset of B cells called B-1b B cells. Mice expressing an inducible form of the gene encoding TSLP had abundant autoantibodies, which were synthesized by B-1b cells and B cells from the spleen. These mice displayed early symptoms of renal disease owing to damage caused by the accumulation of these autoantibodies in kidney tissues.
TSLP expression is linked to inflammatory allergic responses. The authors' findings suggest that chronic stimulation by TSLP might contribute to the development of antibody-mediated autoimmune diseases.
Local increase in thymic stromal lymphopoietin induces systemic alterations in B cell development
Alexander Astrakhan, Miyuki Omori, Thuc Nguyen, Shirly Becker-Herman, Masanori Iseki, Theingi Aye, Kelly Hudkins, James Dooley, Andrew Farr, Charles E Alpers, Steven F Ziegler & David J Rawlings
Published online: 1 April 2007 | doi 10.1038/ni1452
How one's own DNA can cause autoimmunity
A study in the May issue of Nature Immunology may shed light on the cause of immune activation associated with systemic lupus erythematosus (SLE) — the second most common autoimmune disease in humans.
Found more often in women than in men, SLE is associated with the abnormal production of antibodies that 'attack' normal molecules in the body, including a person�s own DNA. As a result, debilitating inflammation, including skin rashes, hypertension, arthritis, and kidney and nervous system problems, ensues. Anthony Coyle and colleagues studied a protein called HMGB1 that normally binds to DNA in the cell nucleus. HMGB1 is also found in blood plasma, where it can bind to DNA released from dying cells. In many SLE patients, such DNA is also often the target of 'abnormal' lupus antibodies. As a result, antibody-HMGB1-DNA protein complexes form. The new study by Coyle and colleagues finds that antibody-HMGB1-DNA complexes in blood plasma from SLE patients can stimulate immune cells to produce potent inflammatory proteins associated with autoimmunity.
By demonstrating a role for HMGB1 in SLE inflammation, Coyle and colleagues provide unique insight into the pathogenesis associated with increasingly prevalent autoimmune diseases such as SLE. However, whether blocking the inflammatory function of HMGB1 will help SLE patients remains a question for future investigation.
Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE
Jane Tian, Ana Maria Avalos, Su-Yau Mao, Bo Chen, Kannaki Senthil, Herren Wu, Peggy Parroche, Stacey Drabic, Douglas Golenbock, Cherilyn Sirois, Jing Hua, Ling Ling An, Laurent Audoly, Greg La Rosa, Angelika Bierhaus, Peter Naworth, Ann Marshak-Rothstein, Mary K Crow, Katherine A Fitzgerald, Eicke Latz, Peter A Kiener & Anthony J Coyle
Published online: 8 April 2007 | doi 10.1038/ni1457
