CHRONIC STRESS ENHANCES AUTOIMMUNITY EXPANDING IMMUNE CELLS AND INCREASING THE RECRUITMENTCD4+ T CELLS TO TARGET ORGANS

MORENO-SOSA MT; PENNACCHIO GE; PIETROBON EO; YÚDICA F; NEIRA FJ; SOAJE M; VALDEZ SR; JAHN GA; J.P. MACKERN-OBERTI

Congreso; XXXIV Reunión Científica Anual de la sociedad de Biología de Cuyo; 2016

Immune cells can be modulated by several neuroendocrine mediators. It is known that stress may influence the immune system and even be associated to relapses of autoimmune diseases. The aim of this work was to evaluate whether exposure to stress worsens autoimmunity in the NOD (non-obese diabetic) mice which developsspontaneous Type 1 diabetes. To this end, twelve weeks old female NOD mice (n=6; two experiments) were subjected to 60 days of chronic variable stress (CVS) while female NOD control group remained untreated (UT, n=10; two experiments). CVS protocol consists in 5 stressful stimuli, isolation, restraint, illumination, 45° inclination and forced swim test. Disease severity was evaluated by the assessment splenomegaly and leukocyte infiltration ofthe pancreas. At the end of the protocol, mice were euthanized and spleens were weighed while pancreas were minced and stained by monoclonal antibodies against CD45 (pan-leukocyte marker) and CD4 (T cell marker). We found that CVS group showed an increase in the spleen weight compared to UT (UT,119±7 vs CVS 166±35; t test; p< 0,05). In addition, CVS group showed an increase in the CD45+ cell population in the pancreas compared to the UT group (UT 0,779±0,122 vs CVS 2,169±0,50; t test; p< 0,05). Furthermore, the CVS group displayed a 3,2 foldincrease in CD4+ T cell infiltration of the pancreas compared to the UT group (UT 0,207±0,039 vs CVS 0,673±0,196; t test; p< 0,05). In conclusion, these results suggest that CVS increases leukocytes and T helper cells recruitment to the pancreas as well as expands immune cells as measured by spleen increase. Our data support the notion that stress plays a crucial role in autoimmune progression, promoting the study of hypothalamic-pituitaryadrenal axis as a target for new immunotherapeutic designs.