CD127+ CD94+ innate lymphoid cells expressing granulysin and perforin are expanded in patients with Crohn’s disease
Krabbendam, L.; Heesters, B. A.; Kradolfer, C. M.A.; Haverkate, N. J.E.; Becker, M. A.J.; Buskens, C. J.; Bemelman, W. A.; Bernink, J. H.; Spits, H.
(2021) Nature Communications, volume 12, issue 1, pp. 1 - 11
(Article)
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
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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.
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Keywords: Antigens, Differentiation, T-Lymphocyte/genetics, Cells, Cultured, Crohn Disease/genetics, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Immunity, Innate/genetics, Inflammation/immunology, Interleukin-7 Receptor alpha Subunit/metabolism, Lymphocytes/immunology, NK Cell Lectin-Like Receptor Subfamily D/metabolism, Perforin/genetics, Real-Time Polymerase Chain Reaction
ISSN: 2041-1723
Publisher: Nature Publishing Group
Note: Funding Information: The authors thank B. Hooibrink, T.M.M. van Capel, and K.I.M Brandwijk for help with flow cytometry. We thank staff of the Bloemenhove clinic in Heemstede, the Netherlands, for fetal tissues; and Dr. K. Weijer and Drs. Ing. E. Siteur van Rijnstra for processing fetal material. This work was supported by The European Research Council (Advanced grant 341038 to H. Spits), Veni fellowship of the NOW (Netherlands Organization for Sciences (91618032 to B.A. Heesters), ZonMw Veni fellowship (09.150.161.810.107 to J.H. Bernink) and Dutch Lung Fund grant (4.2.18.237JO to J.H. Bernink) Publisher Copyright: © 2021, The Author(s).
(Peer reviewed)
