B cells influence sex specificity of arthritis via myeloid suppressors and chemokines in humanized mice

Marshall Behrens, David Luckey, Harvinder Luthra, Chella David, Veena D Taneja

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Rheumatoid arthritis (RA) occurs two times more often in women than men. B cell depletion has been shown to be efficacious in treating RA. Our previous studies suggested that antigen presentation via B cells results in a sex-specific immune response in DR4 and DR4/DQ8 mice. Here we evaluated the mechanism of efficacy of the B cell depletion in treating arthritis-susceptible DQ8 mice. The data show that arthritic DQ8 mice treated with anti-CD20 antibody in therapeutic protocols show milder disease severity in females as compared to males, which is associated with decreased antibodies to citrullinated proteins and reduced levels of IL-23 and CCL5. Treatment led to significantly increased numbers of T regulatory and monocyte-derived suppressor F4/80+Gr1hi cells in females as compared to male DQ8 mice. Our observations suggest that therapeutic strategies that target B cells may benefit females while functions of DCs might be relatively more important for men than women.

Original languageEnglish (US)
JournalClinical Immunology
DOIs
StateAccepted/In press - Mar 24 2015

Fingerprint

Chemokines
Arthritis
B-Lymphocytes
Rheumatoid Arthritis
Interleukin-23
Antigen Presentation
Monocytes
Anti-Idiotypic Antibodies
Therapeutics
Antibodies
Proteins

Keywords

  • Collagen-induced arthritis
  • Humanized mice
  • Myeloid suppressor cells
  • Rheumatoid arthritis
  • Rituximab
  • T regulatory

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

B cells influence sex specificity of arthritis via myeloid suppressors and chemokines in humanized mice. / Behrens, Marshall; Luckey, David; Luthra, Harvinder; David, Chella; Taneja, Veena D.

In: Clinical Immunology, 24.03.2015.

Research output: Contribution to journalArticle

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abstract = "Rheumatoid arthritis (RA) occurs two times more often in women than men. B cell depletion has been shown to be efficacious in treating RA. Our previous studies suggested that antigen presentation via B cells results in a sex-specific immune response in DR4 and DR4/DQ8 mice. Here we evaluated the mechanism of efficacy of the B cell depletion in treating arthritis-susceptible DQ8 mice. The data show that arthritic DQ8 mice treated with anti-CD20 antibody in therapeutic protocols show milder disease severity in females as compared to males, which is associated with decreased antibodies to citrullinated proteins and reduced levels of IL-23 and CCL5. Treatment led to significantly increased numbers of T regulatory and monocyte-derived suppressor F4/80+Gr1hi cells in females as compared to male DQ8 mice. Our observations suggest that therapeutic strategies that target B cells may benefit females while functions of DCs might be relatively more important for men than women.",
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