Blockade of lymphotoxin pathway exacerbates autoimmune arthritis by enhancing the Th1 response

Shuhua Han, Xuejun Zhang, Ekaterina Marinova, Zeynep Ozen, Roy Bheekha-Escura, Linjie Guo, Daniel Wansley, George Booth, Yang Xin Fu, Biao Zheng

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24 Scopus citations

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. LTα-deficient and wild-type C57BL/6 mice were immunized with CII Male DBA/1 mice were immunized with CII and treated with LTβ receptor immunoglobulin fusion protein (LT/βR-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 LTα-deficient mice was more severe and prolonged than that which developed in wild-type mice. Blocking LT signaling with LTβR-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. Conclusion. 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.

Original languageEnglish (US)
Pages (from-to)3202-3209
Number of pages8
JournalArthritis and rheumatism
Volume52
Issue number10
DOIs
StatePublished - Oct 1 2005

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

Han, S., Zhang, X., Marinova, E., Ozen, Z., Bheekha-Escura, R., Guo, L., Wansley, D., Booth, G., Fu, Y. X., & Zheng, B. (2005). Blockade of lymphotoxin pathway exacerbates autoimmune arthritis by enhancing the Th1 response. Arthritis and rheumatism, 52(10), 3202-3209. https://doi.org/10.1002/art.21341