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Leukocyte Trafficking in Homeostasis and Disease

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Leukocyte trafficking spans a wide variety of migratory processes including: (i) cells involved in the first-line immune defense such as neutrophils and monocytes; (ii) lymphocyte recirculation and (iii) immunosurveillance through lymphoid tissues. Furthermore, it includes the process of lymphocyte migration ...

Leukocyte trafficking spans a wide variety of migratory processes including: (i) cells involved in the first-line immune defense such as neutrophils and monocytes; (ii) lymphocyte recirculation and (iii) immunosurveillance through lymphoid tissues. Furthermore, it includes the process of lymphocyte migration into inflamed tissues and resolution of inflammatory processes, as well as in the migration of hematopoietic precursors into and out of various lymphoid organs such as the bone marrow (BM). However, this trafficking also involves the uncontrolled migration of immune cells during inflammatory pathologies, as well as in the homing of neoplastic cells to BM and lymph nodes. Diapedesis of immune and neoplastic cells across the endothelia and perivascular cells is facilitated by chemokines, cytokines and adhesion molecules, such as selectins and integrins, which act in concert in tightly regulating directional cell motility.

State-of-the-art intravital microscopic technologies using animal models have provided a spatio-temporal view of immune and neoplastic cell trafficking, and are proving crucial for the development of therapies in autoimmune diseases and hematological cancers. Neutrophils, monocytes and subsequently, T lymphocytes, migrate to inflamed tissues to perform immune functions prior to the resolution of inflammation. This process involves inflammatory and immunosuppressive mediators, chemokines and adhesion receptors. Lymphocyte trafficking into and out of lymphoid tissues is controlled by defined sets of chemokines which spatially distribute T and B lymphocytes to gain access to antigens exposed on dendritic cells or to help T cell function. Furthermore, B cell maturation in lymphoid tissues and the homing of plasma cells in the BM also involves cell motility. Likewise, lymphocyte emigration from lymphoid tissues to the blood is controlled by chemotactic molecules which inhibit or facilitate this emigration. The orchestration of leukocyte migration is therefore fundamental to maintain defense and tissue homeostasis. In contrast, deregulated leukocyte trafficking contributes to inflammatory pathologies, including intestinal and neural inflammation. Importantly, the trafficking of immune cells, such as HSCs and neutrophils, has been shown to be regulated by circadian rhythms that play crucial roles in physiology and are important regulators of specific immune functions. Finally, it has also been demonstrated that neoplastic immune cells such as malignant plasma cells in multiple myeloma and leukemia cells, home to and traffic between different immune niches such as the BM and lymph nodes.

In this Research Topic, we welcome the submission of Review and Mini-Review articles which will provide an up-to-date view of different molecular players that regulate key trafficking processes during cell differentiation, immune response and lymphocyte recirculation, as well as in inflammatory pathologies and hematological malignancies.


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