Potential role of IL-17-producing iNKT cells in type 1 diabetes.
We explored in this study the status and potential role of IL-17-producing iNKT cells (iNKT17) in type 1 diabetes (T1D) by analyzing these cells in patients with T1D, and in NOD mice, a mouse model for T1D. Our analysis in mice showed an increase of iNKT17 cells in NOD vs control C57BL/6 mice, partly due to a better survival of these cells in the periphery. We also found a higher frequency of these cells in autoimmune-targeted organs with the occurrence of diabetes, suggesting their implication in the disease development. In humans, though absent in fresh PMBCs, iNKT17 cells are detected in vitro with a higher frequency in T1D patients compared to control subjects in the presence of the proinflammatory cytokine IL-1β, known to contribute to diabetes occurrence. These IL-1β-stimulated iNKT cells from T1D patients keep their potential to produce IFN-γ, a cytokine that drives islet β-cell destruction, but not IL-4, with a reverse picture observed in healthy volunteers. On the whole, our results argue in favour of a potential role of IL-17-producing iNKT cells in T1D and suggest that inflammation in T1D patients could induce a Th1/Th17 cytokine secretion profile in iNKT cells promoting disease development.
Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France; INSERM UMR1160, Paris, France.
Shamin
S
Li
Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France; INSERM UMR1160, Paris, France.
Claudine
C
Joseph
Univ Paris Descartes, Sorbonne Paris Cité, Institut Cochin, Paris, France; INSERM U1016, Paris, France.
Chantal
C
Becourt
Département de Bactériologie, Institut Pasteur, Paris, France.
Jihene
J
Klibi
Univ Paris Descartes, Sorbonne Paris Cité, Institut Cochin, Paris, France; INSERM U1016, Paris, France.
Sandrine
S
Luce
Univ Paris Descartes, Sorbonne Paris Cité, Institut Cochin, Paris, France; INSERM U1016, Paris, France; Service de Diabétologie, Hôtel Dieu, GH Cochin-Hôtel Dieu-Broca, APHP et Univ Paris Descartes, Paris, France.
Daniele
D
Dubois-Laforgue
Univ Paris Descartes, Sorbonne Paris Cité, Institut Cochin, Paris, France; INSERM U1016, Paris, France; Service de Diabétologie, Hôtel Dieu, GH Cochin-Hôtel Dieu-Broca, APHP et Univ Paris Descartes, Paris, France.
Etienne
E
Larger
Univ Paris Descartes, Sorbonne Paris Cité, Institut Cochin, Paris, France; INSERM U1016, Paris, France; Service de Diabétologie, Hôtel Dieu, GH Cochin-Hôtel Dieu-Broca, APHP et Univ Paris Descartes, Paris, France.
Christian
C
Boitard
Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France; INSERM UMR1160, Paris, France.
Kamel
K
Benlagha
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD
D020381:Interleukin-17