title: Cis association of galectin-9 with Tim-3 differentially regulates IL-12/IL-23 expressions in monocytes via TLR signaling.
abstract: Human monocytes/macrophages (M/M(Ф)) of the innate immunity sense and respond to microbial products via specific receptor coupling with stimulatory (such as TLR) and inhibitory (such as Tim-3) receptors. Current models imply that Tim-3 expression on M/M(Ø) can deliver negative signaling to TLR-mediated IL-12 expression through trans association with its ligand Galectin-9 (Gal-9) presented by other cells. However, Gal-9 is also expressed within M/M(Ø), and the effect of intracellular Gal-9 on Tim-3 activities and inflammatory responses in the same M/M(Ø) remains unknown. In this study, our data suggest that Tim-3 and IL-12/IL-23 gene transcriptions are regulated by enhanced or silenced Gal-9 expression within monocytes through synergizing with TLR signaling. Additionally, TLR activation facilitates Gal-9/Tim-3 cis association within the same M/M(Ø) to differentially regulate IL-12/IL-23 expressions through STAT-3 phosphorylation. These results reveal a ligand (Gal-9) compartment-dependent regulatory effect on receptor (Tim-3) activities and inflammatory responses via TLR pathways--a novel mechanism underlying cellular responses to external or internal cues.
authors: Department of Internal Medicine, Division of Infectious Diseases, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, United States of America.
authors: Cheng J
authors: CJ
authors: Ma
authors: Guang Y
authors: GY
authors: Li
authors: Yong Q
authors: YQ
authors: Cheng
authors: Jia M
authors: JM
authors: Wang
authors: Ruo S
authors: RS
authors: Ying
authors: Lei
authors: L
authors: Shi
authors: Xiao Y
authors: XY
authors: Wu
authors: Toshiro
authors: T
authors: Niki
authors: Mitsumi
authors: M
authors: Hirashima
authors: Chuan F
authors: CF
authors: Li
authors: Jonathan P
authors: JP
authors: Moorman
authors: Zhi Q
authors: ZQ
authors: Yao
mesh_terms: D002460:Cell Line; D037161:Galectins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics*; D053759:Interleukin-23 / Q000235:genetics*; D042541:Intracellular Space / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D037161:Galectins; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D053759:Interleukin-23; C105032:LGALS9 protein, human; D008565:Membrane Proteins; D050796:STAT3 Transcription Factor; D051193:Toll-Like Receptors; D018664:Interleukin-12
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