title: Exacerbation of experimental autoimmune encephalomyelitis in the absence of breast regression protein 39/chitinase 3-like 1.
abstract: We previously reported that YKL-40, the human analog of mouse breast regression protein 39 ([BRP-39] chitinase 3like 1), is elevated in the cerebrospinal fluid of patients with a variety of neuroinflammatory conditions, such as multiple sclerosis and traumatic brain injury. Expression of YKL-40 in the CNS was predominantly associated with reactive astrocytes in the vicinity of inflammatory lesions. Because previous studies have shown that reactive astrocytes play a critical role in limiting immune infiltration in the mouse model of experimental autoimmune encephalomyelitis, we explored the role of BRP-39 in regulatingneuroinflammation in experimental autoimmune encephalomyelitis. Using BRP-39--deficient (BRP-39(-/-)) mice, we demonstrate the importance of BRP-39 in modulating the severity of clinical experimentalautoimmune encephalomyelitis and CNS neuroinflammation. At disease onset, absence of BRP-39 had little effect on clinical disease orlymphocytic infiltrate, but by 14 days after immunization, differences in clinical scores were evident. By 28 days after immunization, BRP-39(-/-) mice showed more severe and persistent clinical disease than BRP-39(+/+) controls. Histopathological evaluation showed that BRP-39(-/-) mice had more marked lymphocytic and macrophage infiltrates and gliosis versus BRP-39(+/+) mice. These findings support the role of BRP-39 expression in limiting immune cell infiltration into the CNS and offer a new target to modulate neuroinflammation.
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. dafnabb@yahoo.com
authors.forename: Dafna
authors.initials: D
authors.lastname: Bonneh-Barkay
authors.forename: Guoji
authors.initials: G
authors.lastname: Wang
authors.forename: William A
authors.initials: WA
authors.lastname: Laframboise
authors.forename: Clayton A
authors.initials: CA
authors.lastname: Wiley
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Bissel
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D000071451:Chitinase-3-Like Protein 1; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005911:Gliosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains
chemical_list: C509289:Chil1 protein, mouse; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins