Epithelial cells induce the polar migration via the MHC-I-AltR interaction to eliminate transformed cells

Abstract

In epithelial tissues, adjacent normal cells recognize and eliminate transformed cells, maintaining tissue homeostasis. We have demonstrated that the interaction between MHC-I (Major Histocompatibility Complex Class I) on transformed cells and the receptor AltR (Suboptimal Alteration Recognizing Protein) on the normal epithelial cell plays a central role in triggering the elimination ability within normal cells. Moreover, previous reports have suggested that the collective movement of surrounding normal cells including "non-adjacent peripheral normal cells" which are located further out from transformed cells also contributes to the elimination of transformed cells. However, how the direct interaction mediated by MHC-I-AltR affects the behavior of these peripheral normal cells remained unclear. In this study, we aimed to analyze the relationship between the collective movement of normal cells and the elimination of transformed cells. To achieve this, we visualized the two-dimensional movement of individual epithelial cells using the PIV (Particle Image Velocimetry) analysis and quantified the behavior of transformed cells and surrounding normal cells as vectors composed of speed and direction. As a result, we observed that a subset of normal cells near the transformed cells exhibited the unidirectional migration toward the transformed cells (polar migration), which ultimately led to their elimination. Furthermore, this polar migration was suggested to be induced by the MHC-I-AltR interaction. Additional analyses suggest that MHC-I-stimulated AltR induces Ca2+ signaling between normal cells, which in turn triggers the polar migration. Based on these findings, we conclude that the core molecules involved in transformed recognition, MHC-I and AltR, not only trigger the elimination ability in adjacent normal cells but also regulate the behavior of non-adjacent peripheral normal cells, contributing to the elimination of transformed cells.