A role for the B-cell CD74/macrophage migration inhibitory factor pathway in the immunomodulation of systemic lupus erythematosus by a therapeutic tolerogenic peptide.
Systemic lupus erythematosus (SLE) is an autoimmune disease that involves dysregulation of B and T cells. A tolerogenic peptide, designated hCDR1, ameliorates disease manifestations in SLE-afflicted mice. In the present study, the effect of treatment with hCDR1 on the CD74/macrophage migration inhibitory factor (MIF) pathway was studied. We report here that B lymphocytes from SLE-afflicted mice express relatively elevated levels of CD74, compared with B cells from healthy mice. CD74 is a receptor found in complex with CD44, and it binds the pro-inflammatory cytokine MIF. The latter components were also up-regulated in B cells from the diseased mice, and treatment with hCDR1 resulted in their down-regulation and in reduced B-cell survival. Furthermore, up-regulation of CD74 and CD44 expression was detected in brain hippocampi and kidneys, two target organs in SLE. Treatment with hCDR1 diminished the expression of those molecules to the levels determined for young healthy mice. These results suggest that the CD74/MIF pathway plays an important role in lupus pathology.
Lapter
Smadar
S
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Ben-David
Hava
H
Sharabi
Amir
A
Zinger
Heidy
H
Telerman
Alona
A
Gordin
Maya
M
Leng
Lin
L
Bucala
Richard
R
Shachar
Idit
I
Mozes
Edna
E
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D056747:Immunomodulation; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008814:Mice, Inbred NZB; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology
D000944:Antigens, Differentiation, B-Lymphocyte; D001324:Autoantigens; C063762:CDR1 protein, human; D000949:Histocompatibility Antigens Class II; D008263:Macrophage Migration-Inhibitory Factors; D009419:Nerve Tissue Proteins; D010455:Peptides; C045084:invariant chain; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human