Contribution of dendritic cell/T cell interactions to triggering and maintaining autoimmunity

Abstract

Under healthy conditions, there is a balance between tolerance to self-tissue constituents and immunity against foreign antigens. Autoimmunity diseases (AD) take place when that equilibrium is disrupted and the immune response is directed to self-antigens, leading to injury or destruction of host tissues. The mechanisms conducing to the loss of immune tolerance remain largely unknown. The recent appearance of biological therapies has contributed to signifi cant reduction in morbidity. However, currently available therapies are associated with important side effects and work only as palliative treatments. Dendritic cells (DCs) have emerged as key players in developing and maintaining adaptive immunity due to their capacity to prime and modulate T cell function. Therefore, because DCs work as central modulators of immune tolerance, it is likely that alterations in their function can lead to the onset of autoimmune-infl ammatory diseases. By modulating DC function, novel pathways in antigen-specifi c tolerance could be established. In this article, the possible contribution of altered DC-T cell interactions to the onset of autoimmunity are discussed. In addition, we expand on the notion that some of the functions of these cells could be relevant targets for intervening therapies aimed to restore the balance or even prevent the loss of tolerance.

Innate Immune Cells' Contribution to Systemic Lupus Erythematosus

“…Mature DCs can activate T cells. In contrast, tolerogenic (immature) DCs or monocytes, cells able to differentiate to DCs, can promote T-cell hyporesponsiveness, and induce immune tolerance (46). Therefore, tolerogenic DCs or monocytes have emerged as an attractive therapeutic target, because they can induce antigen-specific tolerance without provoking general, widespread immunosuppression.…”

Targeting Dendritic Cell Function during Systemic Autoimmunity to Restore Tolerance

“…Similarly, peripheral tolerance to tissue specific antigens could be achieved by the homeostatic presentation of autoantigens by immature DCs in the draining lymph node [ 216 ]. Different immune cell interactions could take place in lymph nodes to promote tolerance [ 217 , 218 ]. It has been demonstrated that in lymph nodes from NOD mice, Tregs prevent the interaction and cell arrest of effector T cells with DCs, reducing autoimmune responses [ 217 ].…”

Vitamin C inhibited FasL-induced apoptotic death of mouse dendritic cells through c-FLIP expression

“…Dendritic cells (DCs) are the most potent antigen-presenting cells in the immune system. After capture of foreign antigens, they migrate to the lymphoid organs where DCs become mature and present antigens to naïve T cells to elicit the effective adaptive immune response (Llanos et al, 2011;Xuan et al, 2016). These mature DCs are then induced to undergo apoptosis and disappear from the lymph nodes (LNs) (Llanos et al, 2011;Xuan et al, 2016).…”

“…After capture of foreign antigens, they migrate to the lymphoid organs where DCs become mature and present antigens to naïve T cells to elicit the effective adaptive immune response (Llanos et al, 2011;Xuan et al, 2016). These mature DCs are then induced to undergo apoptosis and disappear from the lymph nodes (LNs) (Llanos et al, 2011;Xuan et al, 2016). The apoptosis is initiated through two major apoptotic pathways: the death receptor-mediated extrinsic pathway and the mitochondrial-involved intrinsic pathway (Martino, 2007).…”