Leukotriene B₄ modulation of murine dendritic cells affects adaptive immunity.

Dendritic cells (DCs) link innate and adaptive immunity. The microenvironment generated during the innate immunity affects DCs and the type of adaptive immunity generated. Lipid mediators are released early in inflammation and could modify the functional state of DCs. Leukotriene B <sub>4</sub> (LTB <sub>4</sub> ) has a wide range of effects on macrophages and in the present study we investigated if it also affects DCs. Murine bone marrow-derived DCs were employed and it was found that stimulation of DCs with LTB4 (10 nM) increased the gene expression of the high affinity receptor BLT-1 but not of BLT-2. It also increased the co-stimulatory molecule CD86 expression but did not affect CD80 and CD40. LTB <sub>4</sub> -stimulated DCs acquired the capacity to present antigen to T lymphocytes, evidenced by antigen-specific proliferation of CD4 <sup>+</sup> lymphocytes in co-cultures of ovalbumin-loaded DCs with DO11.10 splenocytes. LTB <sub>4</sub> -stimulated DCs induced Treg proliferation and increased Th2 cytokine IL-13 in the co-cultures. Expression of transcription factor genes, Gata3 and Foxp3 (Th2 and Treg, respectively) were also found increased. However, the expression of Th1 transcription factor (Tbet) and Th17 (RorγT) were not affected. These results indicate that LTB <sub>4</sub> affects DCs and modulates the type of adaptive immune response