Critical Role for Inflammatory Macrophages in Driving Antigen-dependent Th17 Cell Responses

Macrophages have a key role in regulating immune responses such as inflammation, wound healing, and maintenance of tissue homeostasis. Macrophages are characterized by remarkable plasticity and diversity. They rapidly respond to microenvironmental signals, for example, cytokines and acquire distinct phenotypes and functions. Key phenotypes have been characterized in vitro , as M1-activated proinflammatory/microbicidal macrophages induced by microbial products and IFNg, and, M2 antiinflammatory/ tissue healing/immunomodulatory macrophages induced by IL-4/IL-13/IL-10. These are, however, extremes on a continuum of the phenotypes found in vivo .

Critical Role for Inflammatory Macrophages

The nature and balance of macrophage activation-states is important and their dysregulation has been linked to inflammatory diseases, autoimmunity or, at the other extreme, cancer and chronic wounds. Macrophages are professional antigen-presenting cells (APCs) and recent evidence suggests the heterogeneous nature of macrophages impacts their role in CD4+ Tcell polarization.

CD4+ T helper (Th) cells orchestrate adaptive immune responses. Soluble and cell-contact dependent signals from APCs result in T cell differentiation into distinct functional phenotypes including Th1, Th2, Th17, and regulatory T (Treg) cells, characterised by cytokine output and transcription factor expression. Human M1 and M2 subsets differentially produce cytokines modulating T-cell polarization.