title: Blockade of lymphotoxin pathway exacerbates autoimmune arthritis by enhancing the Th1 response.
abstract: OBJECTIVE
  To study the role of the lymphotoxin (LT) signaling pathway in the development and pathogenesis of collagen-induced arthritis (CIA), and to understand the mechanisms by which blockade of the LT pathway influences the arthritogenic response to type II collagen (CII).
  
  
  METHODS
  LTalpha-deficient and wild-type C57BL/6 mice were immunized with CII. Male DBA/1 mice were immunized with CII and treated with LTbeta receptor immunoglobulin fusion protein (LTbetaR-Ig) or control Ig. Mice were monitored for the development and severity of arthritis. The effects of LT blockade on immune responses were evaluated by cytokine production and antigen-specific proliferation in vitro, the delayed-type hypersensitivity (DTH) response, and serum levels of CII-specific antibodies.
  
  
  RESULTS
  CIA that developed in LTalpha-deficient mice was more severe and prolonged than that which developed in wild-type mice. Blocking LT signaling with LTbetaR-Ig significantly exacerbated the disease. Exacerbation of CIA was associated with an enhanced Th1-type response, including increased type 1 cytokine production, an enhanced DTH response, and elevated production of CII-specific IgG2a antibodies.
  
  
  CONCLUSIONS
  Blockade of the LT signaling pathway exacerbates the development and progression of CIA, probably by skewing the Th1/Th2 balance that determines the outcome of autoimmune responses.
authors.affiliation: Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Han
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Marinova
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Ozen
authors.forename: Roy
authors.initials: R
authors.lastname: Bheekha-Escura
authors.forename: Linjie
authors.initials: L
authors.lastname: Guo
authors.forename: Daniel
authors.initials: D
authors.lastname: Wansley
authors.forename: George
authors.initials: G
authors.lastname: Booth
authors.forename: Yang-Xin
authors.initials: YX
authors.lastname: Fu
authors.forename: Biao
authors.initials: B
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
chemical_list: D008233:Lymphotoxin-alpha; D011948:Receptors, Antigen, T-Cell