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

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.

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