Abstract
A growing number of monogenic immune-mediated diseases have been related to genes involved in pathways of actin cytoskeleton remodeling. Increasing evidences associate cytoskeleton defects to autoinflammatory diseases and primary immunodeficiencies. We reviewed the pathways of actin cytoskeleton remodeling in order to identify inflammatory and immunological manifestations associated to pathological variants. We list more than twenty monogenic diseases, ranging from pure autoinflammatory conditions as familial Mediterranean fever, mevalonate kinase deficiency and PAPA syndrome, to classic and novel primary immunodeficiencies as Wiskott-Aldrich syndrome and DOCK8 deficiency, characterized by the presence of concomitant inflammatory and autoimmune manifestations, such as vasculitis and cytopenia, to severe and recurrent infections. We classify these disorders according to the role of the mutant gene in actin cytoskeleton remodeling, and in particular as disorders of transcription, elongation, branching and activation of actin. This expanding field of rare immune disorders offers a new perspective to all immunologists to better understand the physiological and pathological role of actin cytoskeleton in cells of innate and adaptive immunity.
Highlights
Actin is a family of globular proteins that form microfilaments of cell cytoskeleton
DOCK2 is mainly expressed in peripheral blood leukocytes and DOCK2 deficiency causes an early-onset primary immunodeficiency (PID) characterized by a T-cell defective chemotactic responses with bacterial and viral infections [80]
DOCK8 is a Cell division control protein 42 homolog (Cdc42)-specific guanine nucleotide exchange factor (GEF) that regulates interstitial migration of dendritic cells and DOCK8 deficiency causes the Autosomal recessive (AR) Hyper-IgE syndrome (HIES), a combined immunodeficiency characterized by recurrent viral infections, early-onset malignancy and atopic dermatitis
Summary
Actin is a family of globular proteins that form microfilaments of cell cytoskeleton. The most important function of actin was related to the binding of myosin, collaborating to the muscle contraction with troponin. These properties can be tested adding pure myosin to water and actin, causing an increase in viscosity and birefringence of the liquid due to the formation of the actomyosin complex [1]. A growing number of disorders of the immune system have been linked to actin cytoskeleton abnormalities (numbers are related to the Table 1 and Figure 1) [3]. Evidences that actin cytoskeletal deregulation in immune cells causes inflammatory
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