The Cytoskeleton in T Cell Migration and Activation

About this Research Topic

Background

Factors that regulate the cytoskeleton are necessary for proper immune responses, as seen in humans and mice lacking formins, actin branching factors, actin capping and severing enzymes, microtubule components, etc. These factors regulate the shape and mechanics of T cells as they flow through blood vessels, crawl through tissues, and interact with other cells. Much remains to be learned about how the families of cytoskeletal components (actin, microtubules, intermediate filaments, septins, and motors) dynamically interact and mediate directed movements, modulate signaling pathways, transmit forces to the nucleus, reorganize organelles, and regulate cellular differentiation.

Circulating T lymphocytes adopt marked cell shape alterations when patrolling in the organism to perform immune surveillance. In the blood stream, they adopt a round morphology and are very rigid, most likely to resist the high shear forces. However, when sensing the presence of chemokine signals at the vicinity of organs such as lymph nodes, T cells rapidly become elongated and polarized to cross the blood vessels and enter the tissues. They thus exhibit a very efficient mode of migration by maintaining an asymmetry between the front and the back in search for foreign antigen. Upon contact with antigen-presenting cells (APCs) bearing a cognate peptide, T lymphocytes polarize and alter their morphology to optimize the surface of contact with APCs. Altogether, these different morphologies are controlled by the T cell cytoskeleton and are absolutely crucial for immune function.

The four families of components (actin, microtubules, intermediate filaments and septins) constitute the core of the cytoskeleton. In addition, T cells also use other cytoskeletal proteins such as myosins, cross-linkers and regulators which provide an exquisite plasticity in shape alterations in order to allow T lymphocytes to rapidly adapt to an ever changing environment. Although some progress has been made in the past to better characterize the role of the cytoskeleton in T cell physiology, there is still a need to better understand how all these numerous cytoskeletal elements integrate extracellular signals and work in concert to control T cell morphology and ensure proper T cell function.

In this Research Topic, we aim to present Original Research, Review and Perspective articles dedicated to the latest advances in research on the T cell cytoskeleton. Areas to be covered may include, but are not restricted to:

• Biophysical aspects, super-resolution microscopy and studies of single molecule diffusion at the cell surface controlled by the underlying T lymphocyte cytoskeleton.
• Signaling pathways (RHO GTPases, second messengers, phosphorylation…) involved in the control of the cytoskeleton.
• Role of the various components of the T cell cytoskeleton in physiological and pathological conditions.
• Mouse models deficient for cytoskeletal proteins and patients with rare immune diseases due to mutations in genes encoding for cytoskeletal components.
• Mechanobiology as it relates to the cytoskeleton: the sensing of forces, the conversion of forces to biochemical signals, the transmission of forces from the cytoskeleton to the nucleus, the sensing and modulation of extracellular matrix components by T cells
• Evolutionary aspects of cytoskeleton development in immune cells

Keywords: T lymphocyte, cytoskeleton, migration and antigen recognition, signaling, mechanobiology, biophysics, chemokines, immune diseases

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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