POTENTIAL USAGE OF NK CELLS AND NKG2D-POSITIVE LYMPHOCYTES AS TARGETS IN THERAPY OF CROHN’S DISEASE

Abstract

Autoimmune mechanisms of Crohn’s disease have been extensively studied, following discovery of NOD2, ATG16L1, IRGM genetic polymorphisms associated with Crohn’s disease. These genes play an important role in innate immune response against intracellular bacteria, in particular, due to their direct participation in a process known as autophagy. Due to mentioned genetic traits, the CD patients are more susceptible to chronic infections caused by intracellular pathogens. Recent studies revealed high incidence of intracellular infection with Mycobacterium paratuberculosis and E. coli in the intestinal tissue specimens and blood macrophages obtained from the CD patients. Such a chronic, non-resolved infection may disturb the immune cell properties and affect the balance of pro-inflammatory and anti-inflammatory cytokines, thus resulting into chronic inflammation, a hallmark of Crohn disease.In this view, potential usage of NK cells aimed for influencing macrophage activity represents a new approach in understanding and treatment of autoimmune pathologies. The macrophages are controlled by NK cells. I.e., binding of NKG2D receptor to the MICA molecules on the macrophage surface causes their lysis.A signal transfer via NKG2D receptor may increase functional activity of NK against defective macrophages, and hence, promote their elimination. Moreover, in Crohn patients with usually elevated NKG2D+ lymphocyte numbers, a stimulation of NKG2D+ cells by soluble MICA (sMICA) may influence the balance between cytotoxic and regulatory lymphocytes, and reduce pro-inflammatory cytokine secretion, in order to attenuate chronic inflammation of gut tissues. This review is aimed to discuss a role of NKG2D+ NK cells in Crohn’s disease pathology and their possible implications for management and treatment of this disorder.

Keywords

• nkg2d
• nk
• mica
• macrophages
• autoimmunity
• crohn’s disease