New insights into thyroid hormone action on dendritic cells (DC) function

ALAMINO VA; MONTESINOS, MM; MASCANFRONI ID; GIGENA N; RABINOVICH GA; MASINI-REPISO AM; PELLIZAS, CG

Lima

Congreso; XIV Latin American Thyroid Congress; 2011

Latin American Thyroid Society

Background: We reported the expression of thyroid hormone receptors in mice DC, the main antigen (Ag)-presenting cells, and a role of physiological T3 levels promoting DC maturation and T cell allostimulatory capacity directing a T1-type response (FASEB J 2008,22:1032) involving PI3K- independent Akt and NFkB activation signals (JBC 2010,285:9569). Moreover, T3 increased DC ability to stimulate a cytotoxic Ag-specific response and Ag cross-presentation (RAEM 2010,47:77). Objectives: We further explored: 1) the inflammatory cytokine profile of T3- stimulated DC and its splenocyte stimulatory capability and 2) the ability of T4 to mimic T3- induced effects on DC. Methods: DC were pulsed with T3 (5 nM) or T4 (10-9-10-5M) for 18 h Intracellular and secreted cytokine production was assayed by flow cytometry and ELISA respectively. The ability of treated-DC to stimulate allogenic splenocytes was assessed in a mixed lymphocyte reaction. P<0.05 was considered statistically significant (ANOVA, Student-Neuman- Keuls). Results: 1) T3 stimulated DC production of TNF-a and IL-6. Allogeneic splenocytes co- cultured with T3-stimulated DC secreted higher levels of IL-17 and expressed lower levels of FoxP3 vs control DC. 2) T4 was unable to stimulate IL-12 DC production. Conclusions: Our findings provide evidence for a critical role of T3 in the induction of Th17 polarization (cells that bolster anti-tumor responses by enhancing cytotoxic Tcell activity) in addition to the Th1 profile Furthermore, T3 decreased regulatory T lymphocytes revealed by a reduction of CD4+FoxP3+ cells. In turn, T4 did not reproduce T3 reported effects. These findings confer to T3 adjuvant properties with profound implications in immunotherapy including DC antitumor vaccines.