Galectin-9 expands immunosuppressive macrophages to ameliorate T-cell-mediated lung inflammation.
Galectin-9 (Gal-9) plays pivotal roles in the modulation of innate and adaptive immunity to suppress T-cell-mediated autoimmune models. However, it remains unclear if Gal-9 plays a suppressive role for T-cell function in non-autoimmune disease models. We assessed the effects of Gal-9 on experimental hypersensitivity pneumonitis induced by Trichosporon asahii. When Gal-9 was given subcutaneously to C57BL/6 mice at the time of challenge with T. asahii, it significantly suppressed T. asahii-induced lung inflammation, as the levels of IL-1, IL-6, IFN-gamma, and IL-17 were significantly reduced in the BALF of Gal-9-treated mice. Moreover, co-culture of anti-CD3-stimulated CD4 T cells with BALF cells harvested from Gal-9-treated mice on day 1 resulted in diminished CD4 T-cell proliferation and decreased levels of IFN-gamma and IL-17. CD11b(+)Ly-6C(high)F4/80(+) BALF Mphi expanded by Gal-9 were responsible for the suppression. We further found in vitro that Gal-9, only in the presence of T. asahii, expands CD11b(+)Ly-6C(high)F4/80(+) cells from BM cells, and the cells suppress T-cell proliferation and IFN-gamma and IL-17 production. The present results indicate that Gal-9 expands immunosuppressive CD11b(+)Ly-6C(high) Mphi to ameliorate Th1/Th17 cell-mediated hypersensitivity pneumonitis.
Arikawa
Tomohiro
T
Departments of Immunology and Immunopathology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Saita
Naoki
N
Oomizu
Souichi
S
Ueno
Masaki
M
Matsukawa
Akihiro
A
Katoh
Shigeki
S
Kojima
Keisuke
K
Nagahara
Keiko
K
Miyake
Minoru
M
Yamauchi
Akira
A
Kohrogi
Hirotsugu
H
Hirashima
Mitsuomi
M
D000818:Animals; D000950:Antigens, Ly / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D005434:Flow Cytometry; D037161:Galectins / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D014250:Trichosporon / Q000254:growth & development / Q000276:immunology
D000950:Antigens, Ly; D039481:CD11b Antigen; D037161:Galectins; D007375:Interleukin-1; D020381:Interleukin-17; D015850:Interleukin-6; C494192:Ly-6C antigen, mouse; D011994:Recombinant Proteins; D007371:Interferon-gamma