Role of stromal‐cell derived factor‐1 in the development of autoimmune diseases in non‐obese diabetic mice

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Abstract
Summary: 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− B220low CD38+ CD43+ CD23− progenitor B cells and IgM+ IgD+ B220high 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.