While the etiopathogenesis of rheumatoid arthritis (RA) is unknown, it has been proposed that the combination of genetic and environmental factors is involved in RA development. Genetic susceptibility in association with environmental factors trigger the immune responses and activate the innate and acquired immune system. Due to the anatomical, neurological and biochemical situation of the joints, immune complexes, and activated immune cells finally enter the joint, and immune system activation causes inflammation and damage to the articular tissues.
Although there are many cells at the site of joint inflammation, fibroblast-like synoviocyte (FLS) cells are one of the most prominent inflammatory cells in the joint environment. FLS cells are directly responsible for the destruction of the cartilage, causing inflammation and autoimmunity. These cells play important roles in many pathological processes in the synovium.
Due to inflammatory conditions and cellular destruction in joints, it seems endogenous molecules through tissue damage present to immune cells and triggers the immune system via TLR-4. TLR-4 activation leads to chronic inflammation in RA. We are interested in how targeting TLR4 of FLS cells control chronic inflammation in joints and alleviate the inflammatory condition of RA patients.
Ankylosing spondylitis (AS) is an autoimmune and inflammatory disease, in which the immune cells become hyperactive and identify self antigens. Increased production of inflammatory cytokines is involved in the pathogenesis of the disease.
Natural killer (NK) cells comprise about 5-15% of peripheral blood mononuclear cells, are involved in killing target cells by secreting granules containing perforin, granzyme, and granolysin. The number of NK cells correlates with the AS Disease Activity Index (BASDAI) score. Moreover, a decrease in the number of regulatory T (Treg) cells and impairment of their function in AS patients have been implicated.
Regarding the important role of killing activity of NK and Treg cells in AS disease, my hypothesis of dissertation aims to evaluate the levels of NK and Treg cells expressing perforin, granzyme, and granulysin, as well as exhaustion and cytotoxicity of NK cells in the etiopathogenesis of AS disease. I exert fellow-cytometry as well as molecular experiments to come up with comprehension of NK and Treg cells mechanobiology in etiopathogenesis of AS disease.