Phenotypic and Functional Changes in Peripheral Blood Natural Killer Cells in Crohn Disease Patients

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.

Prior Food-Induced Allergic Gut Inflammation Leading To Multiple Food Allergies in C57Bl/6 Mice

“…The same was observed in the villus IEC/IEL ratio, where EXP-2, EXP-3 and POS CONT showed significant lower ratios than NEG CONT and EXP-1. This IEC/IEL ratio reduction occurs due to increased proliferation of leucocytes in the lamina propria and massive infiltration in epithelium as already observed [69][70][71] .…”

Deep Analysis of the Peripheral Immune System in IBD Reveals New Insight in Disease Subtyping and Response to Monotherapy or Combination Therapy

“…Furthermore, they demonstrated that blood NK cells were activated and generally more poised to migrate to the gut in treatment-naïve CD patients as compared with control subjects. 15 As we observed reduced numbers of NK cells, independent of active inflammation (albeit in non-treatment-naïve UC and CD patients) this might suggest an increase in NK cell egress to the gut. NK cells may play a proinflammatory role, being a primary source of IFNg, important in the skewing toward Th1 response.…”

“…Our results are generally consistent with previous reports implicating NK cells in IBD. While Samarani et al 15 demonstrated increased levels of blood NK cells in treatment-naïve CD patients relative to control subjects, they did observe a reduction in specific blood NK subsets such as CD56 bright CD16 low . Furthermore, they demonstrated that blood NK cells were activated and generally more poised to migrate to the gut in treatment-naïve CD patients as compared with control subjects.…”

“…Figure15. Association of anti-TNF and thiopurine monotherapy or combination therapy in IBD patients for ratios between FACS-defined immune cell types and CBC.…”

Targeting NK Cells to Enhance Melanoma Response to Immunotherapies

“…There are three NCRs expressed on human NK cells: NCR1 (NKp46/CD335), NCR2 (NKp44/CD336) and NCR3 (NKp30/CD337). While NCR1 and NCR3 are constitutively expressed on resting NK cells [ 20 , 21 , 22 ], NCR2 is only induced upon NK cell activation [ 23 ].…”