Growth hormone prevents the development of autoimmune diabetes

Ricardo Villares, Dimitri Kakabadse, Yasmina Juarranz, Rosa P. Gomariz, Carlos Martínez-A, and Mario Mellado

PNAS November 26, 2013 110 (48) E4619-E4627; https://doi.org/10.1073/pnas.1314985110

1. Edited by Tak W. Mak, The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute at Princess Margaret Hospital, University Health Network, Toronto, ON, Canada, approved October 18 2013 (received for review August 9, 2013)

Abstract

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.