IMPACT OF IMT504 ON THE IMMUNE SYSTEM OF FEMALE NON-OBESE DIABETIC (NOD/Ltj) MICE

S BIANCHI; V MARTINEZ ALLO; C LIBERTUN; M TOSCANO; VA LUX-LANTOS; MS BIANCHI

Ciudad Autónoma de Buenos Aires

Congreso; reunión Conjunta de Sociedades de Biociencias; 2017

Immunomodulatoryoligonucleotide IMT504 (IMT) improved glycemia, beta cell function, and reducedleukocyte islet infiltration in spontaneous autoimmune diabetic mice (femaleNOD/Ltj). We analyzed the effects of IMT on immune parameters. Femalediabetic NOD/LtJ mice (two consecutive glycemia levels (Gly) ≥ 250 mg/dl) weretreated daily with IMT for five days (20mg/kg/day) or saline as control (DC). Theday following the last injection, fasted Gly was measured and mice weresacrificed. Pancreatic leukocytes and splenocytes were obtained, immune cellpopulations (by flow cytometry) and cytokines expression (by q PCR) wereanalyzed respectively. DC mice showed 11% (2/19) spontaneous reversion of thediabetic condition whereas IMT treatment improved Gly in 72% of mice (13/18) (χ2:DC vs IMT20: p<0.01). IMTtreatment significantly diminished Gly at day 6 [(mg/dl): IMT20: Day 1:307.92±34.7 vs Day 6: 230.08±97.6, p<0.001]. Pancreas CD45+leukocytes showed a near significant reduction in IMT vs DC [DC CD45+%: 8.4±5.9 vs IMT CD45+%: 3.83±2.14, p=0.06]. CD4+, CD8+, B220+, Cd11c+, F4/80+ andFOXP3+ population did not show significant differences. With IMT treatment,spleen IL12p40 expression showed a significant increase [DC: 1.27±0.18 vs IMT:3.91±1.26, p<0.01]; while TNF-alpha expression showed a near significant decrease[DC: 1.33±0.52 vs IMT: 0.81±0.51, p=0.07]. IFN-gamma, IL4, and IL10 did notshow significant differences. These results confirm that IMT reduced leukocytepancreas infiltration shown by a near significant reduction in CD45+population. Increased IL12p40 subunit  isshared by both IL12 and IL23 cytokyne. IL23 promotes IL17 secretion, which couldhave regulatory effects, considering its inhibition on the apoptosis onsuppressor myeloid cells. These results encourage further investigation onthese cytokines expression (IL23 and IL17), and confirm that IMT modulates theimmune system in NOD/Ltj mice.