In:
The Journal of Immunology, The American Association of Immunologists, Vol. 186, No. 1_Supplement ( 2011-04-01), p. 44.18-44.18
Abstract:
Fibrosis is the end-result of many inflammatory conditions. Using scleroderma-associated interstitial lung disease (SLD) as a model fibrotic disease, we investigated cellular mediators of fibrosis in an open-label trial of imatinib mesylate (imatinib), a tyrosine kinase inhibitor. At baseline, high-resolution computer tomography (HRCT) findings of SLD strongly correlated with plasmacytoid dendritic cells (pDC) and IL-4-producing (IL-4+) T-cells in bronchoalveolar lavage (BAL) from individual lung lobes. pDC and IL-4+ and CD4+ T-cells in BAL correlated with each other, and with molecules CCL24, Nampt, PAI1-active, and PDGF-AB, which can recruit/activate leukocytes, smooth muscle cells and collagen-producing cells. pDCs also correlated with IL-3 and M-CSF. One-year post-imatinib, lung pDC and IL-4+ T-cells were significantly reduced. Interestingly, CD4+ T-cells increased along with soluble ICAM-3 and PECAM-1, except in one patient who showed worsened SLD. Thus we envision a role for pDCs in SLD, and propose that IL-3/M-CSF induce differentiation and maturation of pDCs that mediate local T-cell infiltration and differentiation into IL-4+ T-cells and promote fibrosis. Further elucidation of this axis and how drugs such as imatinib intercept it may identify targets to counter fibrosis that invariably leads to end-organ failure.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.186.Supp.44.18
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2011
detail.hit.zdb_id:
1475085-5
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