The Role of Neutrophils in Transplanted Organs

Abstract

Neutrophils are often viewed as non-specialized effector cells whose presence is a simple indicator of tissue inflammation. There is new evidence that neutrophils exist in subsets and have specialized effector functions that include extracellular trap generation and the stimulation of angiogenesis. The application of intravital imaging to transplanted organs has revealed novel requirements for neutrophil trafficking into graft tissue and illuminated direct interactions between neutrophils and other leukocytes that promote alloimmunity. Paradoxically, retaining some neutrophilia may be important to induce or maintain tolerance. Neutrophils can stimulate anti-inflammatory signals in other phagocytes and release molecules that inhibit T cell activation. Here we will review the available evidence of how neutrophils regulate acute and chronic inflammation in transplanted organs and discuss the possibility of targeting these cells to promote tolerance.

Neutrophil extracellular trap fragments stimulate innate immune responses that prevent lung transplant tolerance

“…Consistent with observations made in rejecting human lung recipients, 48 many of these autoreactive CD4 + T cells expressed IL-17A. As T h 17 cells drive neutrophilia through stimulating the expression of ELR + CXC chemokines and granulopoietic cytokines 49 is supported by R01HL092514.…”

Molecular assessment of rejection and injury in lung transplant biopsies

“…The role of neutrophils in lung injury is of particular interest because lung tissue is characterized by high neutrophil influx compared with hearts or kidneys. 32 The ability to molecularly phenotype small pieces from TBB opens the possibility of establishing the mechanisms of CLAD and being able to predict its development. CLAD is difficult to study because of its variable presentation and lack of histologic definition, and also because it may involve lung compartments that are underrepresented in TBBs (e.g., small airways).…”

Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance

“…As a result, neutrophils have been have been historically viewed as pro-inflammatory cells that protect against intracellular pathogens though the release of extracellular traps (27). In organ transplantation, the role of neutrophils is commonly associated to antibody mediated and chronic rejection or ischemia reperfusion injury and resolution of inflammation (28). However, murine neutrophils also release anti-inflammatory cytokines (29), and recent evidence suggests that neutrophils are able to negatively regulate T cell mediated immune responses (30).…”

“…29 In organ transplantation, the role of neutrophils is commonly associated to antibody mediated and chronic rejection or ischemia reperfusion injury and resolution of inflammation. 30 However, murine neutrophils also release anti-inflammatory cytokines, 31 and recent evidence suggests that neutrophils are able to negatively regulate T cell mediated immune responses. 32 Here, we show that neutrophils favor tolerance by mediating macrophage polarization in the transplanted organ uncovering a previously unrecognized function of neutrophils in the context of organ transplantation.…”