Leukemia inhibitory factor (LIF) modulates the development of dendritic cells in a dual manner.

Objective: Dendritic cells (DCs) are professional antigen presenting cells majorly modulated by various environmental factors. Leukemia inhibitory factor (LIF) is a pleiotropic cytokine from interleukin-6 family. Previous studies demonstrate that LIF is associated with several tolerogenic events; yet the exact effect of this cytokine on the generation and function of DCs was not explicitly identified. Materials and methods: To clarify the role of LIF in DCs development, immature DCs were differentiated from mouse bone marrow (BM) in a GM-CSF and IL-4 containing medium with or without LIF. Afterwards, in maturation process, the differentiated DCs were exposed to TNF-alpha in the presence or absence of LIF. Results: Immature DCs differentiated in the presence of LIF, proved a significant enhancement in the expression of MHCII, CD40, or CD86 molecules and in the antigen uptake function. LIF treatment of normal DCs while stimulating for maturation, caused a significant decrement in the expression of phenotypic markers as well as an increment in the antigen uptake function in comparison with TNF-alpha-only stimulated cells; however, the reduced ability for induction of allogenic T-cell proliferation proved no statistical significance. Conclusions: Our results can reflect a role for LIF in the generation and particularly maturation of DCs. It can be assumed that LIF rather modulates the maturation level, leading to the development of semi-mature and tolerogenic DCs. According to the high levels of LIF in immune-privileged sites like brain and uterine, it seems that the cytokine may account for the formation of local DCs that help the establishment of immunosuppressive environments.