Roche says that the September issue of Nature Immunology reports researchers at Roche Basel in collaboration with immunologists at the Harvard Medical School, Boston, MA have discovered a naturally occurring peptide that could play a pivotal role in the fight against autoimmune diseases.
The so called CLIP (class II associated invariant chain peptide) lowers the production of those cells of the immune system that are critical in triggering pro-inflammatory immune responses, including autoimmunity. This finding may give rise to new therapeutic strategies in particular in the field of rheumatoid arthritis (RA), Roche said in a release.
"RA belongs to the group of autoimmune diseases that depend on the expansion of a subset of blood cells - so called helper T lymphocytes (TH1)," explained Harald Kropshofer, Roche Head Non-clinical Immunology. "Particular TH1 cells contribute to autoimmunity by recognizing proteins of our own body, thereby triggering adverse reactions of the immune system against the body's own tissues. At a certain stage, these TH1 cells begin to secrete hormone-like substances, such as interferon-gamma, interleukin-2 (IL-2) or interleukin-6 (IL-6) that can trigger, mediate and maintain autoimmune diseases. Hence, a peptide that helps to lower the generation rate or abundance of these TH1 cells could be an extremely helpful approach in RA therapy," he added.
Kropshofer's team could show in a series of preclinical studies that specialized cells of the immune system, termed 'dendritic cells', turn on the natural occurring peptide CLIP on the cell surface which reduces the number of helper T cells changing to the TH1 type. Thus, CLIP appeared to function as a novel type of peptide regulator. More important, the researchers found that synthetic CLIP had the same function as naturally occurring CLIP. This opens up the possibility of using synthetic CLIP or variants thereof as therapeutic agents. CLIP mediates its activity by binding to molecules of the major histocompatibility complex (MHC) class II which are being viewed as risk factors for RA and other autoimmune diseases, the release added.
"The potential pharmacological importance of this discovery comes from the fact that modulating levels of CLIP may be used to modulate the immune response itself," said Ira Mellman, Department Head Ludwig Institute of Cancer Research, Yale University, New Haven.
Autoimmune diseases are a number of disorders, most of them serious, resulting from an inappropriate or excessive response by components of the immune system. The cause is a breakdown in the mechanisms controlling immunological tolerance to the body's own tissues. As a result, antibodies or certain T lymphocytes attack the body's own proteins or healthy cells.