title: Dipeptidyl peptidase I regulates the development of collagen-induced arthritis.
abstract: OBJECTIVE
  To examine the role of dipeptidyl peptidase I (DPPI), a widely expressed lysosomal cysteine protease, in the development of collagen-induced arthritis (CIA) in mice.
  
  
  METHODS
  Wild-type (WT) and DPPI-deficient (DPPI(-/-)) mice backcrossed to DBA/1J mice for 10 generations were immunized with bovine type II collagen (CII), and disease susceptibility and severity were assessed over time. Collagen-specific B cell and T cell responses and the production of proinflammatory cytokines (tumor necrosis factor alpha, interleukin-1, and interleukin-6) were measured. In addition, adoptive transfer of splenocytes from WT, CII-sensitized mice was performed to evaluate the specific role of DPPI(-/-) T lymphocytes.
  
  
  RESULTS
  The majority of DPPI(-/-) mice were resistant to CIA induction, although clinical disease (i.e., evidence of inflammation and bone erosions) did develop in a small number of DPPI(-/-) mice. The protection against disease development was not attributable to a defect in the B and T cell response to collagen immunization, because both anticollagen antibody production and T cell proliferation in response to CII were normal. Release of the proinflammatory cytokines was largely unaffected in CII-stimulated DPPI(-/-) splenocytes. In addition, when cells isolated from the joints of DPPI(-/-) mice were stimulated in vitro, they had no intrinsic defect in their ability to release inflammatory cytokines. Last, adoptive transfer of splenocytes from WT, CII-immunized mice into naive WT and DPPI(-/-) mice led to development of arthritis in WT mice but not in DPPI(-/-) mice.
  
  
  CONCLUSIONS
  These results indicate that DPPI regulates a critical step in the development of CIA that is independent of T cell and B cell functions.
authors.affiliation: Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.forename: Christine T N
authors.initials: CT
authors.lastname: Pham
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000917:Antibody Formation; D001169:Arthritis, Experimental / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D020789:Cathepsin C / Q000378:metabolism*; D024043:Collagen Type II / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D006614:Hindlimb; D007111:Immunity, Cellular; D007114:Immunization; D007596:Joints / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D013154:Spleen / Q000378:metabolism / Q000473:pathology
chemical_list: D024043:Collagen Type II; D016207:Cytokines; D020789:Cathepsin C