Identification of soluble TREM-2 in the cerebrospinal fluid and its association with multiple sclerosis and CNS inflammation.
Triggering receptor expressed on myeloid cells 2 (TREM-2) is a membrane-bound receptor expressed by microglia and macrophages. Engagement of TREM-2 on these cells has been reported to reduce inflammatory responses and, in microglial cells, to promote phagocytosis. TREM-2 function is critical within the CNS, as its genetic deficiency in humans causes neurodegeneration with myelin and axonal loss. Blockade of TREM-2 worsened the mouse model for multiple sclerosis. In the present study, a soluble form of TREM-2 protein has been identified by immunoprecipitation and by ELISA. Soluble TREM-2 protein (sTREM-2) was detected in human CSF, and was compared among subjects with relapsing-remitting multiple sclerosis (RR-MS; n = 52), primary progressive multiple sclerosis (PP-MS; n = 21), other inflammatory neurologic diseases (OIND; n = 19), and non-inflammatory neurologic diseases (NIND; n = 41). Compared to NIND subjects, CSF sTREM-2 levels were significantly higher in RR-MS (P = 0.004 by ANOVA) and PP-MS (P < 0.001) subjects, as well as in OIND (P < 0.001) subjects. In contrast, levels of sTREM-2 in blood did not differ among the groups. Furthermore, TREM-2 was detected on a subset of CSF monocytes by flow cytometry, and was also highly expressed on myelin-laden macrophages in eight active demyelinating lesions from four autopsied multiple sclerosis subjects. The elevated levels of sTREM-2 in CSF of multiple sclerosis patients may inhibit the anti-inflammatory function of the membrane-bound receptor suggesting sTREM-2 to be a possible target for future therapies.
Piccio
Laura
L
Department of Neurology and Neurosurgery, Washington University School of Medicine, St Louis, MO 63110, USA. picciol@neuro.wustl.edu
Buonsanti
Cecilia
C
Cella
Marina
M
Tassi
Ilaria
I
Schmidt
Robert E
RE
Fenoglio
Chiara
C
Rinker
John
J
Naismith
Robert T
RT
Panina-Bordignon
Paola
P
Passini
Nadia
N
Galimberti
Daniela
D
Scarpini
Elio
E
Colonna
Marco
M
Cross
Anne H
AH
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism; D004679:Encephalomyelitis / Q000097:blood / Q000134:cerebrospinal fluid* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005487:Foam Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid* / Q000473:pathology; D020528:Multiple Sclerosis, Chronic Progressive / Q000097:blood / Q000134:cerebrospinal fluid / Q000473:pathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000134:cerebrospinal fluid / Q000473:pathology; D011149:Pons / Q000378:metabolism / Q000473:pathology; D011971:Receptors, Immunologic / Q000097:blood; D055815:Young Adult
D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C498715:TREM2 protein, human
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