Abstract

The distinction between innate and adaptive immunity is one of the basic tenets of immunology. The co-operation between these two arms of the immune system is a major determinant of the resistance or susceptibility of the host following pathogen invasion. Hence, this interactive co-operation between cells of the innate and adaptive immunity is of significant interest to immunologists. The sub-population of CD4+ T cells with regulatory phenotype (regulatory T cells; Tregs), which constitute a part of the adaptive immune system, have been widely implicated in the regulation of the immune system and maintenance of immune homeostasis. In the last two decades, there has been an explosion in research describing the role of Tregs and their relevance in several immunopathologies ranging from inflammation to cancer. The majority of these studies focus on the role of Tregs on the cells of the adaptive immune system. Recently, there is significant interest in the role of Tregs on cells of the innate immune system. In this review, we examine the literature on the role of Tregs in immunology. Specifically, we focus on the emerging knowledge of Treg interaction with dendritic cells, macrophages, neutrophils, and γδ T cells. We highlight this interaction as an important link between innate and adaptive immune systems which also indicate the far-reaching role of Tregs in the regulation of immune responses and maintenance of self-tolerance and immune homeostasis.

Highlights

  • The immune system protects the host against pathogen invasion and is armed with an arsenal of deadly ammunition necessary for the elimination of microbes or substances determined to pose significant threat to the normal functioning of the host

  • Lewkowicz et al showed that activated Tregs upregulate the expression of suppressor of cytokine signaling 3 (SOCS 3) in neutrophils and induce IL-10 and TGF-β production [144]

  • We found that Tregs regulate survival and activity of human and murine neutrophils and co-culture of Tregs and neutrophils increases neutrophil apoptosis [150]

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Summary

Introduction

The immune system protects the host against pathogen invasion and is armed with an arsenal of deadly ammunition (cells and proteins) necessary for the elimination of microbes or substances determined to pose significant threat to the normal functioning of the host. The induction of Tregs by DCs has been shown to be mediated through the inhibitory molecule programmed death-ligand 1 (PD-L1) expressed on DCs. genetic or immunological inhibition of PD-L1 on DCs leads to their inability to induce FOXP3+ Tregs even in the presence of the necessary cytokine signals [75]. Laouar et al demonstrated that targeted functional inactivation of TGF-β receptor signaling in DCs resulted in enhanced T cell responses in experimental autoimmune encephalomyelitis (EAE) [94].

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