Evolution of the IL-6/class IB cytokine receptor family in the immune and nervous systems.

It has been suggested that the cytokine receptor has a structure similar to immunoglobulin and this structural similarity has raised the possibility that they have evolved from a common ancestral molecule. In the early 1970s, it was discovered that developing sympathetic neurons could switch from an adrenergic to cholinergic phenotype. The search for a diffusible factor responsible for this eventually led to the identification of leukemia inhibitory factor (LIF). Cholinergic differentiation factor (CDF)/LIF has turned out to belong to the IL-6/class IB cytokine family. In this article we further speculate on a plausible molecular pathway for the IL6/class IB receptor family in the immune and nervous systems. We think that the evolution of the IL-6/class IB receptor family may have occurred in at least two major steps. Firstly, binding subunits of an IL-6 receptor and for a CDF/LIF receptor evolved and secondly, a third binding subunit of a CNTF receptor evolved. Our evolutional consideration predicts that the binding subunits generally determine the specificity of the receptors and it is possible that novel members of the cytokine family and their receptors exist in the nervous system.