Neutrophil trafficking to lymphoid tissues: physiological and pathological implications

Abstract

Recent advances have provided evidence for the involvement of neutrophils in both innate and adaptive immunity, robustly challenging the old dogma that neutrophils are short-lived prototypical innate immune cells solely involved in acute responses to microbes and exerting collateral tissue damage. There is now ample evidence showing that neutrophils can migrate into different compartments of the lymphoid system where they contribute to the orchestration of the activation and/or suppression of lymphocyte effector functions in homeostasis and during chronic inflammation, such as autoimmune disorders and cancer. In support of this notion, neutrophils can generate a wide range of cytokines and other mediators capable of regulating the survival, proliferation and functions of both T and B cells. In addition, neutrophils can directly engage with lymphocytes and promote antigen presentation. Furthermore, there is emerging evidence of the existence of distinct and diverse neutrophil phenotypes with immunomodulatory functions that characterise different pathological conditions, including chronic and autoimmune inflammatory conditions. The aim of this review is to discuss the mechanisms implicated in neutrophil trafficking into the lymphoid system and to provide an overview of the immuno-regulatory functions of neutrophils in health and disease in the context of adaptive immunity. Copyright © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Keywords: adaptive immunity; auto-immunity; cancer; chronic inflammation; lymphatic system; neutrophils.

Figure 1

Neutrophils and the regulation of the adaptive immune response in diseases. Neutrophils have been implicated in the regulation of T and B cell activities in many pathological scenarios including inflammageing, cancer and autoimmune disorders such as RA and SLE. Neutrophils can both stimulate and immunosuppress lymphocyte functions through various mechanisms due to the plasticity of their phenotype, localisation and environmental priming. For instance they can secrete activating cytokines or act as APCs to stimulate lymphocyte proliferation and auto‐antibody production (e.g. via NETosis). In contrast, other sub‐types of neutrophils have been shown to directly inhibit T cell activation through the release of TGFβ, NO and Arg‐1 as well as through the expression and direct engagement of PD‐L1 with T cells.