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Martinez, L. M.

Publications and source records attributed to Martinez, L. M..

2 recordsLinked to original sources

Adaptive and Innate Immune Cell Responses in Tendons and Lymph Nodes After Tendon Injury and Repair

Tendon injuries are a common clinical condition with limited treatment options. The cellular components of the innate system, such as neutrophils and macrophages, have been well studied in tendon injuries. However the adaptive immune system, comprised of specialized lymphocytes, plays an important role in orchestrating the healing of numerous tissues but less is known about these cells in tendon healing. To gain a greater understanding of the biological processes that regulate tendon healing, we sought to determine how the cellular components of the adaptive and innate immune system respond to a tendon injury using two-month old male mice. We determined that the lymphatic vasculature is present in the epitenon and superficial regions of Achilles tendons. We then created an acute Achilles tenotomy followed by repair, and collected tendons and draining lymph nodes one, two, and four weeks after injury. Using flow cytometry and histology, after tendon injury we observed a robust adaptive immune cell response that followed an initial innate immune cell response. There was an accumulation of monocytes, neutrophils, and macrophages one week after injury that declined thereafter. Dendritic cells and CD4+ T cells peaked two weeks after injury, while B cells and CD8+ T cells progressively increased over time. In parallel, immune cells of the draining popliteal lymph node demonstrated a similarly coordinated response to the injury. These results suggest that there is an adaptive immune response to tendon injury and adaptive immune cells may play a role in regulating tendon healing.

physiology

The Notch and EGFR signaling regulate caspase inhibitor Diap1 to match supply with intestinal demand

The regenerative activity of adult stem cells carries a high risk of cancer, particularly in highly renewable tissues. To guarantee that the correct organ size is attained and to cope with the continual risk of cancer, developing tissues often use programmed cell death (PCD) as an adaptive mechanism to cull excess and abnormal cells. Members of the family of Inhibitor of Apoptosis Proteins (IAPs) inhibit caspases and cell death and are often overexpressed in cancer. Here, we show that Diap1 is expressed in committed progenitor (enteroblast) cells in the adult Drosophila intestine. Blocking endogenous caspases uncovered that more than half of enteroblasts produced by intestinal stem cells (ISCs) are actively eliminated by apoptosis in the physiological intestine and also led to tumorigenesis. We find that antagonistic interplay between the Notch and EGFR signaling on Diap1 regulation governs the enteroblast cell death or survival decision via the conserved Klumpfuss/WT1-Lozenge/RUNX axis, which also regulates of differentiation plasticity of enteroblasts. These data provide new insights into how apoptosis drives adult tissue renewal and protection against tumors.

cell biology