# Specific inflammatory stimuli that engage innate immune sensors induce novel CD103 expression profiles in macrophages

## TL;DR

This study shows that macrophages can express CD103 under certain inflammatory conditions, challenging the belief that CD103 is only found on T cells and dendritic cells.

## Contribution

The study reveals that macrophages can upregulate CD103 via p38 MAPK signaling in response to specific inflammatory stimuli.

## Key findings

- CD103 is minimally expressed at baseline in macrophages but is selectively upregulated after stimulation with endosomal TLR agonists.
- p38 MAPK inhibition prevents CD103 upregulation, indicating a role for p38 MAPK signaling in this process.
- In vivo LCMV infection induces CD103 expression on peritoneal macrophages.

## Abstract

The integrin CD103 is an adhesion molecule that facilitates immune cell retention in epithelial tissues through its interaction with E-cadherin. It is a marker for certain CD8+ T-cell subpopulations and conventional type 1 dendritic cells (cDC1), but its presence on macrophages remains poorly characterized. Macrophage differentiation is influenced by M-CSF and GM-CSF, and we investigated whether macrophages can also express CD103 under inflammatory conditions. We examined baseline CD103 expression in bone marrow-derived macrophages (BMDMs) differentiated in M-CSF or GM-CSF and then stimulated them with pathogen-associated molecular patterns (PAMPs) or examined them following viral infection. We found that CD103 is minimally expressed at baseline but is selectively upregulated in M-CSF-differentiated macrophages after stimulation with endosomal TLR agonists. Mechanistically, p38 MAPK inhibition prevented CD103 upregulation, suggesting that this process is mediated by p38 MAPK signaling. Furthermore, in vivo LCMV infection induced CD103 expression on peritoneal macrophages. These findings demonstrate that macrophages can express CD103 under specific inflammatory conditions, challenging the assumption that CD103 is restricted to T cells and dendritic cells. This study expands our understanding of CD103 beyond its recognized roles in T cells and DCs, providing new insight into its regulation by macrophages.