Protein fights inflammatory disease

by Aimee Keenan-Greene

A new study in the Nature Immunology  says a protein that acts as a 'master switch' to determine whether certain white blood cells will boost or dampen inflammation, a finding that may help the search for new drugs for rheumatoid arthritis, as reported by Reuters Health.

Rheumatoid arthritis is predominantly a disease that affects women ages 20 to 60. It usually starts at around 35 with typical estrogen dominant symptoms: general aches and stiffness, particularly in the morning, pain in the joints, fatigue and difficulty sleeping.

The research team included Thomas Krausgruber, Katrina Blazek, Tim Smallie, Saba Alzabin, Marc Feldmann and Irina A Udalova of the Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London, UK.;  Helen Lockstone and Natasha Sahgal from the Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.;  and Tracy Hussell of the National Heart and Lung Institute, Faculty of Medicine, Imperial College of Science, Technology and Medicine, South Kensington Campus, London, UK.

The authors wrote:

" Polymorphisms in the gene encoding the transcription factor IRF5 that lead to higher mRNA expression are associated with many autoimmune diseases. Here we show that IRF5 expression in macrophages was reversibly induced by inflammatory stimuli and contributed to the plasticity of macrophage polarization. High expression of IRF5 was characteristic of M1 macrophages, in which it directly activated transcription of the genes encoding interleukin 12 subunit p40 (IL-12p40), IL-12p35 and IL-23p19 and repressed the gene encoding IL-10. Consequently, those macrophages set up the environment for a potent T helper type 1 (TH1)-TH17 response. Global gene expression analysis demonstrated that exogenous IRF5 upregulated or downregulated expression of established phenotypic markers of M1 or M2 macrophages, respectively. Our data suggest a critical role for IRF5 in M1 macrophage polarization and define a previously unknown function for IRF5 as a transcriptional repressor ".

Other inflammatory diseases include inflammatory bowel disease (IBD), lupus and multiple sclerosis (MS).

IBD, which is not the same thing as irritable bowel syndrome (IBS),  refers to two chronic diseases that cause inflammation of the intestines: ulcerative colitis and Crohn's disease 

Up to 1 million Americans are thought to have IBD, which occurs most often in people ages 15 to 30, but can affect younger kids and older people. 

Lupus is a chronic inflammatory disease that can affect various parts of the body, especially the skin, joints, blood, and kidneys.

Multiple sclerosis is a chronic, often disabling disease that attacks the central nervous system (CNS), which is made up of the brain, spinal cord, and optic nerves. Symptoms may be mild, such as numbness in the limbs, or severe, such as paralysis or loss of vision.