Chemokine Receptor-Dependent Control of Skin Tissue-Resident Memory T Cell Formation

Infection or inflammation of the skin recruits effector CD8⁺ T cells that enter the epidermis and form populations of long-lived tissue-resident memory T (T_RM) cells. These skin T_RM cells migrate within the constrained epidermal environment by extending multiple dynamic dendritic projections and squeezing between keratinocytes to survey the tissue for pathogens. In this study, we examined the signals required for this distinctive mode of T cell migration by inhibiting key cytoskeletal components and performing intravital two-photon microscopy to visualize T_RM cell behavior. We found that T_RM cell motility and dendrite formation required an intact actomyosin cytoskeleton and the Rho-associated coiled-coil containing kinases. We also identified an essential role for microtubules for maintaining skin T_RM cell shape and cellular integrity. We reveal a role for pertussis toxin-sensitive signaling for T_RM cell dendritic morphology and migration that is independent of CXCR3 or CXCR6, or the skin-selective chemokine receptors CCR10 and CCR8. However, we found that CXCR6 and CCR10 expression by CD8⁺ T cells was required for the optimal formation of memory T cell populations, in particular T_RM cell populations in the skin.