Title:MIF and CD74 - Suitability as Clinical Biomarkers
Volume: 14
Issue: 14
Author(s): Gerrit Grieb, Bong-Sung Kim, David Simons, Jurgen Bernhagen and Norbert Pallua
Affiliation:
Keywords:
Biomarker, CD74, macrophage migration inhibitory factor (MIF), macrophage migration inhibitory factor receptor.
Abstract: Macrophage migration inhibitory factor (MIF) is a pleiotropic immunoregulatory cytokine whose effects on
arresting ‘random’ immune cell movement was already recognized decades ago. MIF is quasi-constitutively expressed by
a variety of different cells and tissues, including immune cells such as T-cells and monocytes/macrophages, but also nonimmune
cells like certain endocrine cells and cells lining interior body cavities or contacting the exterior environment,
such as endothelial cells (ECs), or epithelial cells in kidney, gut and skin. Contrary to its historic name, MIF has a direct
chemokine-like function and promotes ‘directed’ cell migration (i.e. chemotaxis) and plays a prominent role in
inflammatory and atherogenic leukocyte recruitment. At the molecular level, these activities are based on a non-cognate
interaction between MIF and the CXC chemokine receptors CXCR2 and CXCR4. Importantly, MIF also interacts with
surface CD74, a type II transmembrane protein, inducing its phosphorylation and the recruitment of CD44, leading
ultimately to ERK1/2 phosphorylation. Multiple studies have pointed to the utility of MIF as a biomarker for different
diseases that have an inflammatory component; these include systemic infections and sepsis, cancer, autoimmune diseases
as well as different metabolic disorders. In this Review, we highlight the suitability of MIF and CD74 as biomarkers for
different disease applications.
