11 - Adaptive and Innate Immunoregulatory Cells

Abstract

In systemic lupus erythematosus (SLE), the impaired immune homeostasis is associated with clinical manifestations that generally affect multiple tissues and organs. The inability to properly suppress proinflammatory events that lead to tissue damage and subsequent loss of organ function is significantly influenced by an ongoing dysfunction of immunoregulatory cell activities (Table 11.1). This is because different types of immune cells display functional abnormalities in SLE, including those endowed with immunoregulatory functions. Indeed, the immune dysfunction in SLE affects checkpoints that are involved in both the effector and regulatory immune responses because of an impairment of the mechanisms of maintenance and/or establishment of immune tolerance. In normal conditions, immunoregulatory cells suppress proinflammatory and effector responses to maintain immune homeostasis (Fig. 11.1). However, in SLE this important mechanism of peripheral immune tolerance to self becomes insufficient in adequately controlling autoimmune reactivity either because of numeric and/or functional deficits of the immunoregulatory cells or because of an acquired inadequacy of these cells to inhibit local mediators and immune cells that sustain and/or amplify inflammation. Different studies have implicated dysfunctional immune regulation at the level of the adaptive and innate immune systems in SLE, and defined phenotypic and functional abnormalities which will be the focus of this chapter. We will also include considerations that while the suppressive activity of immunoregulatory cells is crucial for the inhibition of autoimmune responses and inflammation, additional factors (such as stage of disease) need to be taken into account in the facilitation or reduction of the activity of these cells in SLE.