# Loss of integrin alpha7-mediated signaling induces a dendritic cell-like phenotype in macrophages cultured on laminin-211/221 isoforms

## TL;DR

This study shows that losing integrin alpha7 signaling in macrophages leads to a dendritic cell-like phenotype when cultured on laminin-α2 chains.

## Contribution

The study reveals a novel role of integrin α7 in regulating macrophage differentiation into dendritic cell-like cells via laminin-α2 interactions.

## Key findings

- Loss of integrin α7 signaling induces a dendritic cell-like phenotype in macrophages on laminin-α2.
- Blocking integrin α7 activates AKT through PI3K and increases DC markers and costimulatory molecules.
- Integrin α7 and laminin-α2 may be relevant for dendritic cell immunotherapy.

## Abstract

Laminin comprises α/β/γ subunits and performs tissue-specific functions that control cellular behavior. Laminin-α2 chains are highly expressed in neural components such as glial and Schwann cells and in muscles. Macrophages play important roles in tissue homeostasis and repair, and laminins affect macrophage dynamics. Integrin α7, a transmembrane receptor crucial for regulating cell–matrix interactions, has a high affinity for laminin-α2, but its function in macrophages remains unknown. Here, we find that loss of integrin α7 signaling induces a dendritic cell (DC)-like phenotype in THP-1-derived macrophages and in primary monocytes-derived macrophages induced by granulocyte macrophage colony-stimulating factor cultured on laminin-α2 chains. Functional blocking of integrin α7 induced dendritic processes of THP-1-derived macrophages. Gene expression analysis revealed DC markers and costimulatory molecules, and coculture experiments demonstrated that the DC-like cells could stimulate T cell proliferation. Functional inhibition of integrin α7 decreased PI3K-p85α levels and activated PI3K, thereby activating AKT. Monocyte-derived macrophages cultured on laminin α2 chains decreased integrin α7 expression, exhibited dendritic-like morphology, and increased expression of DC markers and costimulatory molecules. These findings suggest that, besides the established influence of cytokine milieu, DC differentiation is regulated by laminin α2/integrin α7-mediated cell adhesion. Integrin α7 has been a therapeutic target in tumors, and antibody-based integrin α7 neutralization can be clinically useful. The results of this study suggest implications for integrin α7 and laminin-α2 chains in DC immunotherapy.