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.