Differential role of regulatory T cells in early and late stages of pulmonary fibrosis.
Regulatory T cells (Tregs) are a specific subset of T lymphocytes that regulate the function of other subsets of lymphocytes. Contradictory results have been reported regarding the role of Tregs in lung fibrosis. We wished to clarify the role of Tregs in the early and late stages of bleomycin-induced lung fibrosis in mice by depleting them with anti-CD25+ antibody (PC61). Mice treated with PC61 in early stages had significantly decreased number of CD4+CD25+ T cells compared to mice treated with the isotype control. The number of inflammatory cells, the concentrations of collagen, TGFβ1, the content of collagen and hydroxyproline in lung tissue were significantly reduced in PC61-treated mice compared to mice treated with the isotype control group. Pathological examination of the lung also disclosed reduced fibrotic changes and decreased fibrosis score in the PC61 group compared to control group. By contrast, mice treated with PC61 in late stages of the disease showed more infiltration of inflammatory cells and higher fibrotic score and hydroxyproline content in the lungs than mice treated with the isotype control. Our results suggest that Tregs play a detrimental role in early stages but protective role in late stages of pulmonary fibrosis in mice.
Department of Immunology, Mie University, Tsu city, Mie, Japan.
Daniel
D
Boveda-Ruiz
Corina N
CN
D'Alessandro-Gabazza
Masaaki
M
Toda
Takehiro
T
Takagi
Masahiro
M
Naito
Yuki
Y
Matsushima
Takahiro
T
Matsumoto
Tetsu
T
Kobayashi
Paloma
P
Gil-Bernabe
Ayshwarya-Lakshmi
AL
Chelakkot-Govindalayathil
Yasushi
Y
Miyake
Atsushi
A
Yasukawa
John
J
Morser
Osamu
O
Taguchi
Esteban C
EC
Gabazza
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D001761:Bleomycin / Q000008:administration & dosage; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000473:pathology*; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000906:Antibodies; D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D001761:Bleomycin