LAUSR

Maintenance of cell population size is fundamental to the proper functioning of multicellular organisms. Here, we describe a cell-intrinsic cell density–sensing pathway that enabled T cells to reach and maintain an appropriate population size. This pathway operated “kin-to-kin” or between identical or similar T cell populations occupying a niche within a tissue or organ, such as the lymph nodes, spleen, and blood. We showed that this pathway depended on the cell density–dependent abundance of the evolutionarily conserved protein coronin 1, which coordinated prosurvival signaling with the inhibition of cell death until the cell population reached threshold densities. At or above threshold densities, coronin 1 expression peaked and remained stable, thereby resulting in the initiation of apoptosis through kin-to-kin intercellular signaling to return the cell population to the appropriate cell density. This cell population size-controlling pathway was conserved from amoeba to humans, thus providing evidence for the existence of a coronin-regulated, evolutionarily conserved mechanism by which cells are informed of and coordinate their relative population size. Description A mechanism that enables T cells and amoebae to maintain appropriate population sizes is revealed. Crowd control with coronins Peripheral naïve T cells are maintained at near constant numbers. Ndinyanka Fabrice et al. uncovered a pathway involving the protein coronin 1 in regulating T cell population homeostasis. Coronin 1 abundance correlated with T cell density and was higher in lymph nodes than in spleens. Below threshold densities of T cells, coronin 1 suppressed apoptosis through the intracellular retention of surface adhesion molecules. Above threshold densities, coronin 1 abundance was not sufficient to prevent the surface presentation of adhesion molecules and apoptosis. A similar mechanism operated in the amoeba Dictyostelium discoideum that depended on a coronin 1 homolog. Thus, T cells and amoebae intrinsically sense and regulate their population densities through cell density–dependent regulation of coronin abundance.