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 language | English |
|---|---|
| Pages (from-to) | 406-414 |
| Number of pages | 9 |
| Journal | American Journal of Respiratory Cell and Molecular Biology |
| Volume | 48 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2013 |
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Keywords
- Autoimmunity
- B cells
- Bronchus-associated lymphoid tissue
- T cells
ASJC Scopus subject areas
- Cell Biology
- Pulmonary and Respiratory Medicine
- Molecular Biology
- Clinical Biochemistry
Cite this
Autoreactive T and B cells induce the development of bronchus-associated lymphoid tissue in the lung. / Shilling, Rebecca A.; Williams, Jesse W.; Perera, Jason; Berry, Elizabeth; Wu, Qiang; Cummings, Oscar; Sperling, Anne I.; Huang, Haochu.
In: American Journal of Respiratory Cell and Molecular Biology, Vol. 48, No. 4, 04.2013, p. 406-414.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Autoreactive T and B cells induce the development of bronchus-associated lymphoid tissue in the lung
AU - Shilling, Rebecca A.
AU - Williams, Jesse W.
AU - Perera, Jason
AU - Berry, Elizabeth
AU - Wu, Qiang
AU - Cummings, Oscar
AU - Sperling, Anne I.
AU - Huang, Haochu
PY - 2013/4
Y1 - 2013/4
N2 - 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.
AB - 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.
KW - Autoimmunity
KW - B cells
KW - Bronchus-associated lymphoid tissue
KW - T cells
UR - http://www.scopus.com/inward/record.url?scp=84878215388&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878215388&partnerID=8YFLogxK
U2 - 10.1165/rcmb.2012-0065OC
DO - 10.1165/rcmb.2012-0065OC
M3 - Article
C2 - 23371062
AN - SCOPUS:84878215388
VL - 48
SP - 406
EP - 414
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
SN - 1044-1549
IS - 4
ER -