CD127+ CD94+ innate lymphoid cells expressing granulysin and perforin are expanded in patients with Crohn’s disease

L. Krabbendam, B. A. Heesters, C. M. A. Kradolfer, N. J. E. Haverkate, M. A. J. Becker, C. J. Buskens, W. A. Bemelman, J. H. Bernink and H. Spits ()
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L. Krabbendam: University of Amsterdam, Department of Experimental Immunology, Amsterdam Infection & Immunity Institute (AI&II), Cancer Center Amsterdam
B. A. Heesters: University of Amsterdam, Department of Experimental Immunology, Amsterdam Infection & Immunity Institute (AI&II), Cancer Center Amsterdam
C. M. A. Kradolfer: University of Amsterdam, Department of Experimental Immunology, Amsterdam Infection & Immunity Institute (AI&II), Cancer Center Amsterdam
N. J. E. Haverkate: University of Amsterdam, Department of Experimental Immunology, Amsterdam Infection & Immunity Institute (AI&II), Cancer Center Amsterdam
M. A. J. Becker: University of Amsterdam
C. J. Buskens: University of Amsterdam, Department of Experimental Immunology, Amsterdam Infection & Immunity Institute (AI&II), Cancer Center Amsterdam
W. A. Bemelman: University of Amsterdam, Department of Experimental Immunology, Amsterdam Infection & Immunity Institute (AI&II), Cancer Center Amsterdam
J. H. Bernink: University of Amsterdam, Department of Experimental Immunology, Amsterdam Infection & Immunity Institute (AI&II), Cancer Center Amsterdam
H. Spits: University of Amsterdam, Department of Experimental Immunology, Amsterdam Infection & Immunity Institute (AI&II), Cancer Center Amsterdam

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract Phenotypic definition of helper ILC1 and NK cells is problematic due to overlapping markers. Recently we showed the identification of cytotoxic ILC3s characterized by expression of CD94. Here we analyse CD127+ ILCs and NK cells in intestinal lamina propria from healthy donors and Crohn’s disease patients and identify two populations of CD127+CD94+ ILCs, designated population A and B, that can be distinguished on the expression of CD117, CD18 and cytotoxic molecules. Population B expresses granulysin, a cytotoxic molecule linked to bacterial lysis and/or chemotaxis of monocytes. Granulysin protein is secreted by population B cells upon stimulation with IL-15. Activation of population B in the presence of TGF-β strongly reduces the expression of cytotoxic effector molecules of population B. Strikingly, samples from individuals that suffer from active Crohn’s disease display enhanced frequencies of granulysin-expressing effector CD127+CD94+ ILCs in comparison to controls. Thus this study identifies group 1 ILC populations which accumulate in inflamed intestinal tissue of Crohn’s disease patients and may play a role in the pathology of the disease.

Date: 2021
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DOI: 10.1038/s41467-021-26187-x

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