title: Plasma soluble Tim-3 emerges as an inhibitor in sepsis: sepsis contrary to membrane Tim-3 on monocytes.
abstract: Immune dysfunction is the main characteristic of sepsis. T cell Ig and mucin domain protein 3 (Tim-3) on the monocytes has been reported to promote immune homeostasis during sepsis, but the influences of plasm soluble Tim-3 (sTim-3) on the immune system during sepsis remain unknown. Here, 100 patients with different severities of sepsis (40 sepsis, 42 severe sepsis, and 18 septic shock) were enrolled in this study. The Tim-3 and human leukocyte antigen-DR (HLA-DR) on the circulating monocytes were detected using flow cytometry. Plasma sTim-3 was detected by enzyme-linked immunosorbent assay. Inflammatory factors and two kinds of A disintegrin and metalloprotease (ADAM) - ADAM10 and ADAM17 were assessed. The Tim-3 and HLA-DR on the monocytes decreased with increasing sepsis severity. The sTim-3 was reduced in the sepsis and severe sepsis patients but was elevated in the septic shock patients who exhibited significant immunosuppression as predicted by HLA-DR. sTim-3 levels were negatively correlated with IL-12 and TNF-α. ADAM10 and ADAM17, sheddases of Tim-3, exhibited trends toward elevations in the septic shock group. In conclusion, sTim-3 was involved in the development of sepsis. The homeostasis-promoting role of the Tim-3 on the monocytes was disrupted, while the inhibitory role of sTim-3 emerged during sepsis-induced immunosuppression.
authors.affiliation: Department of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing, China.|Joint Logistics Department of Beijing Military Resion, Health Clinic, Beijing First Sanatorium for Retired Officers, Beijing, China.
authors.forename: F
authors.initials: F
authors.lastname: Ren
authors.affiliation: Department of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing, China.|School of Medicine, Nankai University, Tianjin, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Immunology, Beijing Institute of Basic Medical Sciences, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing, China.
authors.forename: K
authors.initials: K
authors.lastname: Xiao
authors.affiliation: Department of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing, China.
authors.forename: D
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry, Chinese PLA General Hospital, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Ai
authors.affiliation: Department of Immunology, Beijing Institute of Basic Medical Sciences, Beijing, China.
authors.forename: C
authors.initials: C
authors.lastname: Hou
authors.affiliation: Department of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Immunology, Beijing Institute of Basic Medical Sciences, Beijing, China.
authors.forename: G
authors.initials: G
authors.lastname: Han
authors.affiliation: Department of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Xie
mesh_terms: D051722:ADAM Proteins / Q000097:blood / Q000276:immunology; D000072197:ADAM10 Protein; D000072198:ADAM17 Protein; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053829:Amyloid Precursor Protein Secretases / Q000097:blood / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D005260:Female; D006684:HLA-DR Antigens / Q000097:blood / Q000276:immunology; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D018664:Interleukin-12 / Q000097:blood / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000097:blood* / Q000276:immunology; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D018805:Sepsis / Q000097:blood* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology
chemical_list: C448908:HAVCR2 protein, human; D006684:HLA-DR Antigens; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human
keywords: immunosuppression; monocytes; sepsis; soluable Tim-3