Molecular Tuning of Actin Dynamics in Leukocyte Migration as Revealed by Immune-Related Actinopathies

Abstract

Motility is a crucial activity of immune cells allowing them to patrol tissues as they differentiate, sample or exchange information, and execute their effector functions. Although all immune cells are highly migratory, each subset is endowed with very distinct motility patterns in accordance with functional specification. Furthermore individual immune cell subsets adapt their motility behaviour to the surrounding tissue environment. This review focuses on how the generation and adaptation of diversified motility patterns in immune cells is sustained by actin cytoskeleton dynamics. In particular, we review the knowledge gained through the study of inborn errors of immunity (IEI) related to actin defects. Such pathologies are unique models that help us to uncover the contribution of individual actin regulators to the migration of immune cells in the context of their development and function.

Constitutively active GPR43 is crucial for proper leukocyte differentiation

“…Since we observed a significant reduction in the expression of β 2 ‐integrin (Mac‐1) components, CD11b and CD18 24 (Figure 5C), the impaired adhesion was at least in part due to the attenuation of these molecules. Motility is important to ensure the immuno‐surveillance action of leukocytes, and the actin cytoskeleton is a prerequisite for this function 25 . In HeLa cells, the enhanced formation of F‐actin filaments was elicited by exogenous expression of HA‐GPR43, but not HA‐GPR41 (Figure 5D).…”

“…Motility is important to ensure the immuno-surveillance action of leukocytes, and the actin cytoskeleton is a prerequisite for this function. 25 In HeLa cells, the enhanced formation of F-actin was elicited by exogenous expression of GPR43, but not HA-GPR41 (Figure 5D). formation was significantly impaired by treatment with GLPG0974 or Y27632, suggesting the involvement of the GPR43/ Gα 12/13 /Rho/ROCK pathway.…”

Immune potency of bioreactor-aged dendritic cells in 3D collagen matrices

“…We have performed mechanobiology studies on T-cell interactions using arti cial APCs, and by varying the stiffnesses of the "synapse" via polyacrylamide gels, we have found differential CD69 expression (unpublished data). It is therefore possible that mDCs cultured on the RPM have altered cytoskeleton dynamics, as reported for other cell types [76], and this mechanically changed the actin-rich synapse of mDCs, affecting the CD69 activation levels on T cells [77].…”

Immune Cell Plasticity in Inflammation: Insights into Description and Regulation of Immune Cell Phenotypes

“…Therefore, it is plausible and likely that both “soft” and “stiff” leukocytes co-exist within different regions of the body, representing different physical phenotypes due to their activation status and actin reorganization processes. Importantly, various pathways have been implicated in the organization and re-organization of the actin cytoskeleton, impacting circulating leukocyte numbers as well as infiltrating leukocyte subsets [ 52 , 53 ]. Another physical–biochemical occurrence is the redistribution of lipid raft signaling platforms [ 54 ].…”