T Lymphocyte Migration: An Action Movie Starring the Actin and Associated Actors

Abstract

The actin cytoskeleton is composed of a dynamic filament meshwork that builds the architecture of the cell to sustain its fundamental properties. This physical structure is characterized by a continuous remodeling, which allows cells to accomplish complex motility steps such as directed migration, crossing of biological barriers, and interaction with other cells. T lymphocytes excel in these motility steps to ensure their immune surveillance duties. In particular, actin cytoskeleton remodeling is a key to facilitate the journey of T lymphocytes through distinct tissue environments and to tune their stop and go behavior during the scanning of antigen-presenting cells. The molecular mechanisms controlling actin cytoskeleton remodeling during T lymphocyte motility have been only partially unraveled, since the function of many actin regulators has not yet been assessed in these cells. Our review aims to integrate the current knowledge into a comprehensive picture of how the actin cytoskeleton drives T lymphocyte migration. We will present the molecular actors that control actin cytoskeleton remodeling, as well as their role in the different T lymphocyte motile steps. We will also highlight which challenges remain to be addressed experimentally and which approaches appear promising to tackle them.

Lymphocyte integrin expression differences between SIRS and sepsis patients

“…From this disease, it has shown that the lack of CD18 causes adhesion and mobility deficiencies that result in multiple skin infections and slow wound healing(36). Consistent with established data, we have shown that CD18 is ubiquitously expressed on all lymphocytes in the peripheral blood(15, 25). The levels of lymphocyte CD18 expression were unchanged by the clinical circumstances with all groups displaying approximately 100% expression.…”

“…T-lymphocytes use integrins to migrate in and out of lymph nodes and, following infection, to migrate into other tissues(14, 17, 18, 25). Integrins are key to the immunological cross-talk between T cells and antigen-presenting cells.…”

“…Integrin β2, CD18, is typically expressed on all lymphocytes(16, 25, 35) with the exception of certain rare immuno-compromised diseases, such as leukocyte adhesion deficiency (LAD)-1 syndrome. From this disease, it has shown that the lack of CD18 causes adhesion and mobility deficiencies that result in multiple skin infections and slow wound healing(36).…”

Clathrin regulates lymphocyte migration by driving actin accumulation at the cellular leading edge

“…Therefore, these data obtained with the amoeboid migration of lymphocytes model confirm the intense relation of clathrin and clathrin‐related proteins with the molecular machinery controlling actin rearrangements. Actin plays a major role in lymphocyte migration (and polarization) by controlling the dynamics of the cell shape during migration . Here, we show a model that integrate the motility signals triggered by the chemokines into coordinated actin rearrangements, being clathrin a key protein in this process that recruits the molecular machinery able to promote actin polymerization, similarly to what was observed in other biological processes .…”

RhoGDI2 positively regulates the Rho GTPases activation in response to the β2 outside-in signaling in T cells adhesion and migration on ICAM-1

“…The migration of T cells is regulated by spatial and temporal cytoskeletal remodeling . Actin filaments are distributed radially in resting T lymphocyte, and polymerize into branches upon chemokine receptor or LFA‐1 engagement .…”