Exacerbation of experimental autoimmune encephalomyelitis in the absence of breast regression protein 39/chitinase 3-like 1

J Neuropathol Exp Neurol. 2012 Nov;71(11):948-58. doi: 10.1097/NEN.0b013e31826eaee7.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / pathology*
  • Chitinase-3-Like Protein 1
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / genetics*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Gliosis / genetics
  • Gliosis / metabolism
  • Gliosis / pathology
  • Glycoproteins / deficiency*
  • Glycoproteins / genetics*
  • Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains


  • Chil1 protein, mouse
  • Chitinase-3-Like Protein 1
  • Glycoproteins