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Pulmonary T cells regulate fibrosis via integrins αVβ3 and αVβ5
Author(s) -
Luzina Irina G.,
Nacu Natalia,
Lockatell Virginia,
Highsmith Kendrick,
Choi Jung,
Todd Nevins W.,
Atamas Sergei P.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1071.8
Subject(s) - integrin , pulmonary fibrosis , fibrosis , t cell , bleomycin , cancer research , pathology , medicine , immunology , chemistry , biology , microbiology and biotechnology , immune system , receptor , chemotherapy
T cells are commonly involved in lung fibrosis, but their mechanistic role is unclear. Lung T cells from patients with scleroderma, idiopathic pulmonary fibrosis, and healthy controls were studied. CCL18 gene delivery in vivo was used to induce selective chemoattraction of T cells to otherwise healthy or bleomycin‐injured mouse lungs. The fibrotic potential of T cells was studied in cell culture. Immunohistologically and flowcytometrically, integrins αVβ3 and αVβ5 were expressed on 32±15% of T cells in patients with fibrosis but not in healthy controls; higher integrin expression levels correlated with worse pulmonary function measures. Levels of mRNAs for these integrins were also increased. Infiltration of T cell in the otherwise healthy mouse lungs was accompanied by integrin expression on T cells, elevated active TGF‐β, and T cell‐dependent collagen accumulation. In contrast, CCL18‐driven infiltration of T cells combined with bleomycin injury showed lack of integrin expression on T cells, lower active TGF‐β, and partial inhibition of collagen accumulation. In vitro overexpression of integrin αVβ3 or αVβ5 on Jurkat cells caused an increase in TGF‐β and collagen in co‐cultures with primary lung fibroblasts. In conclusion, T cells may act pro‐ or antifibrotically, by expressing or not expressing integrins αVβ3 and/or αVβ5, and likely activating or not activating TGF‐β. Support: R01HL074067, VA Merit (SPA).