Role of stromal-cell derived factor-1 in the development of autoimmune diseases in non-obese diabetic mice.
The chemokine stromal-cell derived factor-1 (SDF-1) controls maturation, trafficking, and homing of certain subsets, lymphoid cells including immunogenic B and T cells, as a ligand of the CXCR4 chemokine receptor. Insulin-dependent diabetes mellitus (IDDM) and Sjögren's syndrome (SS), both highly regulated autoimmune diseases, develop spontaneously in non-obese diabetic (NOD) mice. To investigate the role of SDF-1 in the development of autoimmune diseases, we injected groups of NOD female mice with antibodies to SDF-1 (anti-SDF-1), which resulted in a 30% reduction of diabetes up to 30 weeks of age, delayed average diabetes onset by 10 weeks, and suppressed insulitis. Autoimmune sialoadenitis was evident in anti-SDF-1-injected mice (SDF-1-Ig group) at the same level as in all groups of mice, whether injected with non-specific antibodies or not. In addition, in the SDF-1-Ig group, a greater number of immunoglobulin M (IgM)- IgD- B220(low) CD38+ CD43+ CD23- progenitor B cells and IgM+ IgD+ B220(high) CD43- CD38+ CD24+ CD23+ mature B cells remained in the bone marrow, whereas infiltration of mature IgM+ B cells was less extensive in peripheral tissues. Our results suggested that anti-SDF-1 antibodies injection was effective in inhibiting diabetes and insulitis without affecting autoimmune sialoadenitis or SS in NOD mice. SDF-1 may be an essential chemokine for trafficking and migration of autoreactive B cells in the development of diabetes.
Matin
Khairul
K
Department of Oral Science, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8650, Japan.
Salam
M Abdus
MA
Akhter
Joynab
J
Hanada
Nobuhiro
N
Senpuku
Hidenobu
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000473:pathology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D012793:Sialadenitis / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse