T regulatory cells in childhood arthritis – novel insights

Abstract

In recent years, there have been many new developments in the field of regulatory T cells (Treg), challenging the consensus on their behaviour, classification and role(s) in disease. The role Treg might play in autoimmune disease appears to be more complex than previously thought. Here, we discuss the current knowledge of regulatory T cells through animal and human research and illustrate the recent developments in childhood autoimmune arthritis (juvenile idiopathic arthritis (JIA)). Furthermore, this review summarises our understanding of the fields and assesses current and future implications for Treg in the treatment of JIA.

Production of Proinflammatory Cytokines by Monocytes in Liver-Transplanted Recipients with De Novo Autoimmune Hepatitis Is Enhanced and Induces TH1-like Regulatory T Cells

“…Interestingly, while T H 1-like Tregs maintained their immunomodulatory role in liver transplant recipients with normal allograft function, similar to previous reports (33-35), in the setting of inflammation (i.e. in transplant recipients with de novo autoimmune hepatitis), these Tregs lost the ability to suppress effector cell proliferation (Figure 3B-C).…”

“…The function of T H 1-like Tregs has been variably reported as suppressive by some investigators (33-35) and non-suppressive by others (28). Having demonstrated that sorted Tregs from subjects with de novo autoimmune hepatitis lost their immunoregulatory function as well as demonstrating that a pro-inflammatory cytokine milieu within the liver in de novo autoimmune hepatitis can drive IFN-γ secretion from FOXP3 + Tregs, we next questioned if IFN-γ blockade would restore Treg function.…”

Dendritic cells, T cells and their interaction in rheumatoid arthritis

“…These findings imply that iaT reg selectively expand in active disease from T eff , consistent with the origin of T reg type 1 (Tr1) cells [93]. iaT reg may be unsuccessful at restraining these effector responses in vivo due to T eff resistance to T reg -mediated suppression -such as protein kinase B hyperactivation in JIA and secretion of TNF-related apoptosis-inducing ligand (TRAIL) in RA by effector cells -in combination with the proinflammatory milieu [94][95][96][97]. The deep sequencing technologies used for TCR repertoire profiling in these studies are advantageous in that these methods do not rely on prior (auto)antigen knowledge, which poses a major hurdle in autoimmune diseases where multiple putative autoantigens exist or where autoantigens are still yet to be defined [98,99].…”

“…While iaT reg are ontogenically related to the T reg cell lineage, they share substantial TCR repertoire overlap with pathogenic synovial effector T cells (T eff ) and blood CPLs [92]. iaT reg may be unsuccessful at restraining these effector responses in vivo due to T eff resistance to T reg -mediated suppression -such as protein kinase B hyperactivation in JIA and secretion of TNF-related apoptosis-inducing ligand (TRAIL) in RA by effector cells -in combination with the proinflammatory milieu [94][95][96][97]. iaT reg may be unsuccessful at restraining these effector responses in vivo due to T eff resistance to T reg -mediated suppression -such as protein kinase B hyperactivation in JIA and secretion of TNF-related apoptosis-inducing ligand (TRAIL) in RA by effector cells -in combination with the proinflammatory milieu [94][95][96][97].…”

Origin and functions of pro-inflammatory cytokine producing Foxp3+ regulatory T cells

“…RA patients have been reported to exhibit a higher frequency of Th17 like T regs compared to healthy subjects [86]. These T regs also produce IFN-γ, IL-2, ROR-γt and Tbet, along with IL-17A [87,88]. However, the ability of these cells to suppress proliferation, production of IFN-γ and IL-2 in effector T cells was comparable to those of conventional T reg subpopulation from healthy controls, suggesting that these T regs are not reprogrammed to lose their suppressive capacities.…”