title: Recombinant murine calreticulin fragment 39-272 expands CD1d(hi)CD5+ IL-10-secreting B cells that modulate experimental autoimmune encephalomyelitis in C57BL/6 mice.
abstract: Calreticulin (CRT) is a Ca²⁺ binding molecular chaperone in the endoplasmic reticulum, but can also accumulate in soluble form in serum and/or synovial fluid of patients with rheumatic disorders. We have recently shown that a prokaryotically expressed recombinant CRT fragment 39-272 (rCRT/39-272) exhibited potent stimulatory activities against macrophages and B cells. However, intraperitoneal (i.p.) administration of rCRT/39-272 effectively suppressed delayed-type hypersensitivity in mice, attributable to production of anti-CRT Abs favoring Th2 cell differentiation. In this study, we further demonstrate that i.p. injection of rCRT/39-272 reduced disease severity in mouse model of experimental autoimmune encephalomyelitis (EAE), by inhibiting autoantigen-specific Th1 differentiation in vivo. Interestingly, the EAE-modulating effect of rCRT/39-272 was attributed to activation/expansion of CD1d(hi)CD5⁺ IL-10-secreting B (B10) cells rather than induction of CRT-specific antibodies in mice. In vitro, rCRT/39-272 could activate and expand murine splenic B10 cells through a Toll like receptor 4 (TLR4)-dependent pathway. The rCRT-activated B10 cells were able to not only enhance Th2 cell differentiation in vitro but also reduce EAE scores of recipient animals in passive transfer experiments. These results revealed soluble CRT, likely released by tissue cells under stress conditions, as a potentially important multi-faced player in immunoregulation and immunopathological responses.
authors.affiliation: Institute of Biology and Medical Sciences, Soochow University, Suzhou, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Hong
authors.forename: Tengteng
authors.initials: T
authors.lastname: Zhang
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Gao
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000096:biosynthesis*; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018956:CD5 Antigens / Q000096:biosynthesis*; D037282:Calreticulin / Q000502:physiology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D055610:Antigens, CD1d; D018956:CD5 Antigens; D037282:Calreticulin; C526879:Cd1d1 protein, mouse; C526836:Cd5 protein, mouse; C556062:IL10 protein, mouse; D010446:Peptide Fragments; D011994:Recombinant Proteins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D016753:Interleukin-10