Abstract
We investigated activation status, cytotoxic potential, and gut homing ability of the peripheral blood Natural Killer (NK) cells in Crohn disease (CD) patients. For this purpose, we compared the expression of different activating and inhibitory receptors (KIR and non-KIR) and integrins on NK cells as well as their recent degranulation history between the patients and age-matched healthy controls. The study was conducted using freshly obtained peripheral blood samples from the study participants. Multiple color flow cytometry was used for these determinations. Our results show that NK cells from treatment-naïve CD patients expressed higher levels of activating KIR as well as other non-KIR activating receptors vis-à-vis healthy controls. They also showed increased frequencies of the cells expressing these receptors. The expression of several KIR and non-KIR inhibitory receptors tended to decrease compared with the cells from healthy donors. NK cells from the patients also expressed increased levels of different gut-homing integrin molecules and showed a history of increased recent degranulation events both constitutively and in response to their in vitro stimulation. Furthermore, treatment of the patients tended to reverse these NK cell changes. Our results demonstrate unequivocally, for the first time, that peripheral blood NK cells in treatment-naïve CD patients are more activated and are more poised to migrate to the gut compared to their counterpart cells from healthy individuals. Moreover, they show that treatment of the patients tends to normalize their NK cells. The results suggest that NK cells are very likely to play a role in the immunopathogenesis of Crohn disease.
Highlights
Natural Killer (NK) cells are important effector cells of the innate immune system
Significant perturbations were observed in different subsets in Crohn disease (CD) patients compared with the controls: significant decreases were observed in the percentages and numbers of the CD56brightCD16- subset and a significant decrease was noted in the percentage of D56dimCD16+ subsets; a significant increase was observed in the absolute numbers of NK cells of this subset, and significant increases were observed in the percentages and absolute numbers of CD56dimCD16and CD56-CD16+ subsets
We compared the expression of Killer-cell Immunoglobulin-like Receptors (KIRs), various non-KIR molecules, and integrins on peripheral blood NK cells from CD patients and their age-matched healthy control subjects
Summary
Natural Killer (NK) cells are important effector cells of the innate immune system They comprise about 10-15% of the mononuclear cells in the peripheral blood [1,2,3]. NK cells can target and kill autologous cells of the body when the latter become infected with intracellular pathogens (e.g., viruses) and are transformed or stressed due to DNA damage and/or inflammatory stimuli. NK cells can promote autoimmune diseases [6] (reviewed in [7]) They can Mediators of Inflammation regulate immune responses by secreting a variety of soluble mediators such as IFN-γ, TNF-α, GM-CSF, MIP-1α, MIP-1β, and RANTES [8]. They can modulate adaptive immune responses by their interactions with dendritic cells (DC), effector T cells, and Tregs [9, 10]
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