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Int. J. Mol. Sci. 2017, 18(9), 1997;

Anti-NKG2D mAb: A New Treatment for Crohn’s Disease?

Gastro unit, Medical Division, Hvidovre University Hospital, Kettegård Alle 30, DK-2650 Hvidovre, Denmark
Medical Affairs, Janssen Immunology, Janssen-Cilag A/S, Bregnerødvej 133, DK-3460 Birkerød, Denmark
Author to whom correspondence should be addressed.
Received: 13 July 2017 / Revised: 24 August 2017 / Accepted: 11 September 2017 / Published: 16 September 2017
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Crohn’s disease (CD) and ulcerative colitis (UC) are immunologically-mediated, debilitating conditions resulting from destructive inflammation of the gastrointestinal tract. The pathogenesis of IBD is incompletely understood, but is considered to be the result of an abnormal immune response with a wide range of cell types and proteins involved. Natural Killer Group 2D (NKG2D) is an activating receptor constitutively expressed on human Natural Killer (NK), γδ T, mucosal-associated invariant T (MAIT), CD56+ T, and CD8+ T cells. Activation of NKG2D triggers cellular proliferation, cytokine production, and target cell killing. Research into the NKG2D mechanism of action has primarily been focused on cancer and viral infections where cytotoxicity evasion is a concern. In human inflammatory bowel disease (IBD) this system is less characterized, but the ligands have been shown to be highly expressed during intestinal inflammation and the following receptor activation may contribute to tissue degeneration. A recent phase II clinical trial showed that an antibody against NKG2D induced clinical remission of CD in some patients, suggesting NKG2D and its ligands to be of importance in the pathogenesis of CD. This review will describe the receptor and its ligands in intestinal tissues and the clinical potential of blocking NKG2D in Crohn’s disease. View Full-Text
Keywords: Crohn’s Disease; IBD; NKG2D; MICA; MICB; ULBP Crohn’s Disease; IBD; NKG2D; MICA; MICB; ULBP

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Vadstrup, K.; Bendtsen, F. Anti-NKG2D mAb: A New Treatment for Crohn’s Disease? Int. J. Mol. Sci. 2017, 18, 1997.

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