Growth hormone prevents the development of autoimmune diabetes.
Evidence supports a relationship between the neuroendocrine and the immune systems. Data from mice that overexpress or are deficient in growth hormone (GH) indicate that GH stimulates T and B-cell proliferation and Ig synthesis, and enhances maturation of myeloid progenitor cells. The effect of GH on autoimmune pathologies has nonetheless been little studied. Using a murine model of type 1 diabetes, a T-cell-mediated autoimmune disease characterized by immune cell infiltration of pancreatic islets and destruction of insulin-producing β-cells, we observed that sustained GH expression reduced prodromal disease symptoms and eliminated progression to overt diabetes. The effect involves several GH-mediated mechanisms; GH altered the cytokine environment, triggered anti-inflammatory macrophage (M2) polarization, maintained activity of the suppressor T-cell population, and limited Th17 cell plasticity. In addition, GH reduced apoptosis and/or increased the proliferative rate of β-cells. These results support a role for GH in immune response regulation and identify a unique target for therapeutic intervention in type 1 diabetes.
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, E-28049 Madrid, Spain.
Ricardo
R
Villares
Dimitri
D
Kakabadse
Yasmina
Y
Juarranz
Rosa P
RP
Gomariz
Carlos
C
Martínez-A
Mario
M
Mellado
D019264:Adoptive Transfer; D000818:Animals; D016207:Cytokines / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D005434:Flow Cytometry; D013006:Growth Hormone / Q000494:pharmacology*; D007150:Immunohistochemistry; D050417:Insulin-Secreting Cells / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D062706:Prodromal Symptoms; D060888:Real-Time Polymerase Chain Reaction
D016207:Cytokines; D013006:Growth Hormone
Tregs; beta cells