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.

Highlights

  • Understanding how the diverse motility strategies of immune cells are controlled at the molecular level is of paramount importance when investigating immune cell responses in the context of health and disease and when designing cell-based immunotherapies

  • In the context of WASP deficiency, the proportion of immature B cells in the bone marrow (BM) is decreased, while that of transitional B cells in the periphery is increased [77]. Such bias in B cell development has been proposed to result from the defective ability of B cells from Wiskott-Aldrich syndrome (WAS) patients to respond to CXCL12, which plays a major role in immature B cell retention in the BM

  • Results showed that WASP-deficient lymphocytes were unable to form invasive podosomes and failed to migrate through endothelial cells by trans-cellular TEM. These findings suggest that immune cells lacking WASP are restricted to paracellular TEM to exit blood vessel

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Summary

Frontiers in Immunology

All immune cells are highly migratory, each subset is endowed with very distinct motility patterns in accordance with functional specification. 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. 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

INTRODUCTION
Leukocyte Motility Defects in IEIs
SUMMARY OF IDENTIFIED MOTILITY DEFECTS ACROSS ACTINOPATHIES
MOTILITY DEFECTS IN ACTINOPATHIES AT THE ORGANISM LEVEL
Bone Marrow Colonisation and Positioning During Hematopoiesis
Cellular and animal models
RHOG RHOH
Stabilizes WASP
Leukocyte Migration During Thymopoiesis
Leukocyte Homing and Positioning in Secondary Lymphoid Organs
Leukocyte Migration in Peripheral Organs
MOTILITY DEFECTS IN ACTINOPATHIES AT THE TISSUE LEVEL
Adhesion to the Endothelium
Interstitial Migration
Dynamic Assembly of the Immunological Synapse
MOTILITY DEFECTS IN ACTINOPATHIES AT THE ULTRASTRUCTURAL LEVEL
Findings
Nucleus and Organelles
Full Text
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