title: Inhibition of type 1 diabetes correlated to a Lactobacillus johnsonii N6.2-mediated Th17 bias.
abstract: Although it is known that resident gut flora contribute to immune system function and homeostasis, their role in the progression of the autoimmune disease type 1 diabetes (T1D) is poorly understood. Comparison of stool samples isolated from Bio-Breeding rats, a classic model of T1D, shows that distinct bacterial populations reside in spontaneous Bio-Breeding diabetes-prone (BBDP) and Bio-Breeding diabetes-resistant animals. We have previously shown that the oral transfer of Lactobacillus johnsonii strain N6.2 (LjN6.2) from Bio-Breeding diabetes-resistant to BBDP rodents conferred T1D resistance to BBDP rodents, whereas Lactobacillus reuteri strain TD1 did not. In this study, we show that diabetes resistance in LjN6.2-fed BBDP rodents was correlated to a Th17 cell bias within the mesenteric lymph nodes. The Th17 bias was not observed in the non-gut-draining axillary lymph nodes, suggesting that the Th17 bias was because of immune system interactions with LjN6.2 within the mesenteric lymph node. LjN6.2 interactions with the immune system were observed in the spleens of diabetes-resistant, LjN6.2-fed BBDP rats, as they also possessed a Th17 bias in comparison with control or Lactobacillus reuteri strain TD1-fed rats. Using C57BL/6 mouse in vitro assays, we show that LjN6.2 directly mediated enhanced Th17 differentiation of lymphocytes in the presence of TCR stimulation, which required APCs. Finally, we show that footpad vaccination of NOD mice with LjN6.2-pulsed dendritic cells was sufficient to mediate a Th17 bias in vivo. Together, these data suggest an interesting paradigm whereby T1D induction can be circumvented by gut flora-mediated Th17 differentiation.
authors.affiliation: Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Lau
authors.forename: Patrick
authors.initials: P
authors.lastname: Benitez
authors.forename: Alexandria
authors.initials: A
authors.lastname: Ardissone
authors.forename: Tenisha D
authors.initials: TD
authors.lastname: Wilson
authors.forename: Erin L
authors.initials: EL
authors.lastname: Collins
authors.forename: Graciela
authors.initials: G
authors.lastname: Lorca
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Dhyana
authors.initials: D
authors.lastname: Sankar
authors.forename: Clive
authors.initials: C
authors.lastname: Wasserfall
authors.forename: Josef
authors.initials: J
authors.lastname: Neu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Atkinson
authors.forename: Desmond
authors.initials: D
authors.lastname: Shatz
authors.forename: Eric W
authors.initials: EW
authors.lastname: Triplett
authors.forename: Joseph
authors.initials: J
authors.lastname: Larkin
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D041981:Gastrointestinal Tract / Q000276:immunology / Q000382:microbiology; D020381:Interleukin-17 / Q000096:biosynthesis*; D007778:Lactobacillus / Q000276:immunology*; D052200:Limosilactobacillus reuteri / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D051381:Rats; D011913:Rats, Inbred BB; D058504:Th17 Cells / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology
chemical_list: D020381:Interleukin-17