title: Brief Report: Arthritis in KRN T Cell Receptor-Transgenic Mice Does Not Require Interleukin-17 or Th17 Cells.
abstract: Th17 cells and interleukin-17 (IL-17) cytokine family members are implicated in the pathogenesis of many rheumatic diseases. Most studies in mouse models of inflammatory arthritis have demonstrated a key role for the proinflammatory cytokine IL-17A and its receptor, the IL-17 receptor (IL-17R) A/C heterodimer. The aim of this study was to use a rigorous genetic approach to evaluate the contribution of Th17 cells and IL-17 in the autoantibody-dependent KRN T cell receptor-transgenic mouse model of arthritis.
  
  
  
  We bred KRN mice expressing the major histocompatibility complex class II molecule A(g7) (referred to as K/B/g7 mice) and genetically lacking the related cytokines IL-17A and IL-17F or their critical receptor subunit, IL-17RA. Using bone marrow transplantation, we generated mice in which hematopoietic cells from K/B/g7 donor mice lacked the key Th17-differentiating transcription factor, retinoic acid receptor-related orphan nuclear receptor γt (Rorγt).
  
  
  
  K/B/g7 mice lacking both IL-17A and IL-17F produced normal titers of pathogenic autoantibodies, and arthritis developed in a typical manner. Similarly, neither IL-17RA nor Rorγt expression by hematopoietic cells was required for disease development in this model.
  
  
  
  Despite prior reports suggesting that Th17 cells and IL-17A are crucially involved in the pathogenesis of arthritis in K/BxN mice, the results presented here provide genetic evidence that IL-17A and IL-17F, IL-17RA, and Rorγt expression by hematopoietic cells are dispensable for normal arthritis progression in the K/B/g7 mouse model system. We discuss potential explanations for the discrepancies between these 2 highly similar model systems. These findings plus those in other mouse models of arthritis provide insight regarding why therapeutic biologic agents targeting the Th17/IL-17 axis are beneficial in some human rheumatic diseases but not others.
authors.affiliation: University of Minnesota, Minneapolis.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Auger
authors.affiliation: University of Minnesota, Minneapolis.
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Cowan
authors.affiliation: University of Minnesota, Minneapolis.
authors.forename: Brianna J
authors.initials: BJ
authors.lastname: Engelson
authors.affiliation: University of Minnesota, Minneapolis.
authors.forename: Sakeen W
authors.initials: SW
authors.lastname: Kashem
authors.affiliation: Hannover Medical School, Hannover, Germany.
authors.forename: Immo
authors.initials: I
authors.lastname: Prinz
authors.affiliation: University of Minnesota, Minneapolis.
authors.forename: Bryce A
authors.initials: BA
authors.lastname: Binstadt
mesh_terms: D000818:Animals; D020381:Interleukin-17 / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D058504:Th17 Cells / Q000502:physiology*
chemical_list: D020381:Interleukin-17; D011948:Receptors, Antigen, T-Cell