Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

Effects of dietary gluten on murine Natural Killer cell activity  (#92)

Jesper Larsen 1 , Kåre Engkilde 1 , Julie Christine Antvorskov 1 , Christian Weile 1 , Morten Dall 1 , Knud Josefsen 1 , Karsten Buschard 1
  1. The Bartholin Institute, Rigshospitalet, Copenhagen, Denmark

Dietary gluten influences the development of type 1 diabetes (T1D) in non-obese diabetic (NOD) mice2 and biobreeding (BB) rats2, and has been shown to influence a wide range of immunological factors in the pancreas and gut. A recently published case report describes a boy with T1D, who was able to maintain a low fasting blood glucose level without insulin therapy for more than 20 months, while adhering to a gluten free diet since the time of diagnosis3. In this study the effect of gluten on NK cells in vitro and in vivo was studied. 

In vitro gliadin increased direct cytotoxicity and IFN-γ secretion from C57/BL6 splenocytes against MIN6 cells, and gliadin preincubation of MIN6 cells led to a significantly increased proportion of degranulating C57/BL6 CD107a+ NK cells. Stimulation of C57/BL6 purified NK cells with gliadin, increased secretion of TNF-α, IL-2 and IL-10 after only 2 hours of preincubation with MIN6 cells.

In vivo the standard gluten containing diet led to an increase of NKp46+ cells in BALB/c pancreatic lymph nodes (PLN) compared to a GF diet. Finally we found higher expression of the proliferation marker CD71 and activating receptor NKG2D on NKp46+ cells in all lymphoid organs in BALB/c and NOD mice receiving the gluten containing diet. 

We suggest that gluten peptides may activate NK cells locally in the pancreas or gut, which may be important during onset of T1D4. These results represents a possible mechanism for the effect of gluten on T1D, and may help to understand the beneficial effects of a GF diet seen in human disease and animal models of T1D. 

  1. Funda DP, Kaas A, Bock T, Tlaskalová‐Hogenová H, Buschard K (1999). Gluten‐free diet prevents diabetes in NOD mice. Diabetes/metabolism research and reviews 15: 323-327.
  2. Scott FW, Rowsell P, Wang GS, Burghardt K, Kolb H, et al. (2002). Oral exposure to diabetes-promoting food or immunomodulators in neonates alters gut cytokines and diabetes. Diabetes 51: 73-78.
  3. Sildorf SM, Fredheim S, Svensson J, Buschard K (2012). Remission without insulin therapy on gluten-free diet in a 6-year old boy with type 1 diabetes mellitus. BMJ Case Reports
  4. Rodacki M, Svoren B, Butty V, Besse W, Laffel L, et al. (2007). Altered natural killer cells in type 1 diabetic patients. Diabetes 56: 177-185.