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.

Identification of soluble TREM-2 in the cerebrospinal fluid and its association with multiple sclerosis and CNS inflammation / L. Piccio, C. Buonsanti, M. Cella, I. Tassi, R.E. Schmidt, C. Fenoglio, J. Rinker 2nd, R.T. Naismith, P. Panina-Bordignon, N. Passini, D. Galimberti, E. Scarpini, M. Colonna, A.H. Cross. - In: BRAIN. - ISSN 0006-8950. - 131:Part.11(2008 Nov), pp. 3081-3091. [10.1093/brain/awn217]

Identification of soluble TREM-2 in the cerebrospinal fluid and its association with multiple sclerosis and CNS inflammation

L. Piccio
Primo
;
C. Fenoglio;D. Galimberti;E. Scarpini;
2008

Abstract

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.
Immune regulation; Macrophages; Microglia; Multiple sclerosis; Neuroinflammation
Settore MED/26 - Neurologia
nov-2008
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/47459
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