Galectin-8 promotes regulatory T-cell differentiation by modulating IL-2 and TGFβ signaling.
Galectins (Gals) have emerged as potent immunoregulatory molecules that control chronic inflammation through distinct mechanisms. Gal-8, a tandem-repeat type Gal with unique preference for α2,3-sialylated glycans, is ubiquitously expressed, but little is known about its role in T-cell differentiation. Here we report that Gal-8 promotes the polyclonal differentiation of primary mouse regulatory T (Treg) cells in vitro. We further show that Gal-8 also facilitates antigen-specific differentiation of Treg cells, and that Treg cells polarized in the presence of Gal-8 express cytotoxic T-lymphocyte antigen-4 and interleukin (IL)-10 at a higher frequency than control Treg cells, and efficiently inhibit proliferation of activated T-cells in vitro. Investigation of the mechanism by which Gal-8 promotes Treg conversion revealed that Gal-8 activates transforming growth factor-β signaling and promotes sustained IL-2R signaling. Taken together, these data suggest that Gal-8 promotes the differentiation of highly suppressive Treg cells, which has implications for the treatment of inflammatory and autoimmune diseases.
Program in Immunology and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, USA.
James F
JF
Sampson
Department of Ophthalmology, New England Eye Center, Tufts University School of Medicine, Boston, MA, USA.
Amol
A
Suryawanshi
Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, USA.
Wei-Sheng
WS
Chen
Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.|Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
Gabriel A
GA
Rabinovich
Program in Immunology and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, USA.|Department of Ophthalmology, New England Eye Center, Tufts University School of Medicine, Boston, MA, USA.|Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, USA.
Noorjahan
N
Panjwani
D000818:Animals; D060908:CTLA-4 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D037161:Galectins / Q000276:immunology*; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D060908:CTLA-4 Antigen; D037161:Galectins; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta; C526554:galectin-8, mouse; D016753:Interleukin-10