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Differential Frequencies and Functions of NK Cells and CD127 (+) ILC1s in the Terminal Ileum of Crohn’s Disease Patients

Introduction: Crohn’s disease (CD) is a chronic immunemediated disorder of the human gut with an unknown etiology. Traditionally, adaptive immunity has been believed to play a major role in this process. However, emerging evidence also suggests the importance of innate immunity for the pathogenesis of CD.

Methods: We collected surgical terminal ileum samples from 15 CD patients and biopsy terminal ileum samples of an-IL10RA-deficiency-caused-CD patient at different time points. Then we isolated lamina propria mononuclear cells (LPMC) from harvested tissues through enzyme digestion and mechanical dissociation. Finally, we compared the alteration of frequencies and functions of NK cells and CD127(+) ILC1s between inflamed ileums and unaffected ileums of our CD patient cohort by multicolor flow cytometry.

Results: The frequency of NK cells within CD3(-) CD14(-) CD19(-) CD20(-) CD45 (+) CRTH2 (-) LPMCs was significantly increased in the inflamed ileums (51.3%, n=10) compared to unaffected tissues (29.4%, n=5). Then, the frequency of IFN- γ (+) NK cells was also upregulated in the inflamed tissues (34.0%, n=10) compared to control (9.2%, n=5). Further, we observed that the NK cell frequencies were gradually reduced and accompanied by the restoration of normal mucosal architecture in the terminal ileum of our IL10RAdeficiency- caused-CD patient after successful immunosuppressive treatment. In addition, we noticed that the frequency of CD127(+) ILC1s within CD3(-) CD14(-) CD19(-) CD20(-) CD45(+) CRTH2(-) LPMCs was augmented as well in the inflamed tissues (2.2%, n=10) compared to unaffected areas (0.76%, n=5). They were also potent IFN-γ producers.

Conclusions: NK cells and CD127(+) ILC1s displayed differential frequencies and functions in the inflamed terminal ileum of our CD patient cohort. Better understanding of the development, differentiation, phenotypic and functional regulation of these two subsets in the human gut may shed new light on approaches for the modulation of immunity in the future.

Author(s): Jian Li, Andria L Doty, Ying Tang, Dalton Berrie, Atif Iqbal, Sanda A Tan and Sarah C Glover

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