Autoreactive T and B cells induce the development of bronchus-associated lymphoid tissue in the lung

Rebecca A. Shilling, Jesse W. Williams, Jason Perera, Elizabeth Berry, Qiang Wu, Oscar W. Cummings, Anne I. Sperling, Haochu Huang

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Rheumatoid arthritis-related interstitial lung disease (RA-ILD) is associated with significant morbidity and mortality. Studies in humans have found that the incidence of bronchus-associated lymphoid tissue (BALT) correlates with the severity of lung injury. However, the mechanisms underlying the development of BALT during systemic autoimmunity remain unknown. We have determined whether systemic autoimmunity in a murine model of autoimmune arthritis can promote the development of BALT by generating a novel murine model derived from K/BxN mice. Transgenic mice with the KRN T-cell receptor specific for the autoantigen, glucose-6-phosphate isomerase (GPI), were crossed with GPI-specific immunoglobulin heavy and light chain knock-in mice, producing mice with a majority of T andBcells specific for the sameautoantigen.Wefound that67% of these mice demonstrated lymphocytic infiltration in the lungs, localized to either the perivascular or peribronchial regions. Fifty percent of the mice with lymphocytic infiltration manifested lymphoid-like lesions resembling BALT, with distinct T and B cell follicles. The lungs from mice with lymphoid infiltrates hadincreased numbers of cytokine-producing T cells, including IL-17A+ T cells and increased major histocompatibility complex Class II expression on B cells. Interestingly, challenge with bleomycin failed to elicit a significant fibrotic response, compared with wild-type control mice. Our data suggest that systemic autoreactivity promotes ectopic lymphoid tissue development in the lung through the cooperation of autoreactive T and B cells. However, these BALT-like lesions may not be sufficient to promote fibrotic lung disease at steady state or after inflammatory challenge.

Original languageEnglish (US)
Pages (from-to)406-414
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume48
Issue number4
DOIs
StatePublished - Apr 1 2013

Keywords

  • Autoimmunity
  • B cells
  • Bronchus-associated lymphoid tissue
  • T cells

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

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