Nature Reviews Immunology, Published online: 10 September 2025; doi:10.1038/s41577-025-01214-w

The actin cytoskeleton is essential for immune cell shape, signalling and function. In this Review, the authors examine how germ-line mutations affecting actin-regulatory proteins, called immune-related actinopathies, lead to inborn errors of immunity. These are characterized by susceptibility to infection as well as autoimmune and autoinflammatory disease manifestations. Focusing on WASP, HEM1 and DOCK11 deficiencies, the authors examine the diverse mechanisms that link disturbed actin homeostasis in lymphoid and myeloid cells to autoimmunity and autoinflammation and outline emerging mechanistic insights and therapeutic directions.



Summary

This Nature Reviews Immunology article, published September 10, 2025, explores immune-related actinopathies, inborn errors of immunity arising from germ-line mutations affecting actin-regulatory proteins. These mutations disrupt the actin cytoskeleton, crucial for immune cell shape, signaling, and function. The review focuses on deficiencies in WASP, HEM1, and DOCK11, detailing how disturbed actin homeostasis in lymphoid and myeloid cells contributes to both susceptibility to infection and autoimmune/autoinflammatory disease. The authors outline the diverse mechanisms linking actin dysfunction to autoimmunity/autoinflammation, highlighting emerging mechanistic insights and potential therapeutic avenues for these complex conditions.

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