Increased proportion of CD16+ NK cells in the colonic lamina propria of IBD patients but not after Azathioprine treatment.

Alan W Steel (1, 2) , Christopher M Mela (3) , James Oliver Lindsay (4) , Brian G Gazzard (5) , Martin R Goodier (3)

1 Gastroenterology
2 Medicine
3 Immunology
4 Gastroenterology
5 HIV-GUM

Background: Distinct functional subsets of natural killer(NK) cells potentially contribute to the pathology of inflammatory bowel diseases(IBD). Aim: To report the phenotypic and functional characteristics of NK cells in blood and lamina propria(LP) of IBD patients, and the effect of azathioprine. Methods: NK cells from blood and LP of healthy controls(HC) or patients with Crohn's disease(CD), or ulcerative colitis(UC) were studied by flow cytometry. Activation, cytokine production, proliferation and apoptosis of NK cell subsets were studied in-vitro. Results: CD16+NK cells are increased in frequency in the LP comparing CD or UC with HC. Azathioprine therapy was associated with a reduction of total NK cells in blood and LP, preferentially of the CD16+ subset. Azathioprine therapy did not impair NK degranulation, but reduced natural and cytokine activated cytotoxicity and interferon-gamma(IFN-γ production. Culture of resting PBMC with azathioprine resulted in loss of NK cells and inhibition of activation and IFN-γ production. Azathioprine preferentially inhibited proliferation of CD16+ NK cells and induced apoptosis in resting but not in pre-activated NK cells. Conclusions: NK cells with cytolytic potential are enriched in the colonic LP of individuals with IBD. Azathioprine is associated with a reduction in these cells and a normalisation of NK cell populations.

Mots clés: Medicine

Alan W Steel, Christopher M Mela, James Oliver Lindsay, Brian G Gazzard, Martin R Goodier. Increased proportion of CD16+ NK cells in the colonic lamina propria of IBD patients but not after Azathioprine treatment.. Alimentary Pharmacology and Therapeutics, 2010, 33 (1), pp.115. ⟨10.1111/j.1365-2036.2010.04499.x⟩. ⟨hal-00613794⟩