A third subset of ILproducing effector T helper cells, called Th17 cells, has now been discovered and characterized. Here, we summarize. High levels of IL are found in serum and injured tissues during SLE. •. IL sources include both T lymphocytes and innate cells. •. Immune. However, following the description and characterization of IL and Th17 cells, more and more data indicated that these latter types of CD4+.
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Because of these reports, T cells are now recognized as a second critical target of PTH in bone.
The potential pathogenic role of IL-17/Th17 cells in both type 1 and type 2 diabetes mellitus.
Controversy remains on the relative relevance of T cells, osteocytes, and osteoblasts for il 17 and th17 cells activity of PTH. Early studies revealed that levels of PTH typically found in PHPT require the presence of T cells to induce bone loss 2627whereas conditions that cause extreme elevations in PTH levels induce bone loss via T cell-independent mechanisms 28 — TNF stimulates osteoclast formation and activity via multiple mechanisms, which include increased production of RANKL by all osteoblastic cells including osteocytes.
Conditional silencing of the PTH receptor PPR in T cells blunts the stimulation of bone resorption induced by cPTH without affecting bone formation, thus blocking cortical bone loss and converting the effects of cPTH in trabecular bone from catabolic to anabolic These findings demonstrate the critical relevance of direct PPR signaling in T cells.
Th17 cells are the most osteoclastogenic subsets of T cells Th17 cells are defined by their capacity to produce the cytokine IL Th17 cells are constitutively present at mucosal surfaces, especially in the intestinal lamina propria Th17 cells play a pivotal role in the bone loss of inflammatory conditions such as psoriasis, rheumatoid arthritis, il 17 and th17 cells disease, and IBD 40 Therefore, cPTH could expand Th17 cells via several mechanisms.
This reasoning prompted investigations on the relationship between cPTH treatment and Th By contrast, cPTH does not stimulate Th17 cell proliferation The latter experimental model is particularly significant, because the host il 17 and th17 cells possess all physiologic sources of TNF except for T cells.
This il 17 and th17 cells was tested in murine studies that revealed that diltiazem blocks the expansion of Th17 cells, the increase in bone resorption, and the loss of cortical and trabecular bone induced by cPTH.
The finding may suggest a potential therapeutic role for L-type calcium channel blockers in the treatment of hyperparathyroidism.
Analysis of biochemical and histomorphometric indices of bone turnover revealed that neutralization of IL blunts the bone catabolic activity of cPTH by il 17 and th17 cells bone resorption Most recently it was investigated whether IL or IL producing cells play a role in the serum transfer model of arthritis Table 1.
Interestingly, high Il 17 and th17 cells serum levels were observed in transferred arthritic SCID mice, and it was revealed that neutrophils acted as source of IL in the effector phase of arthritis Table 1.
In contrast, either systemic or local intra-articular adenoviral gene transfer of IL exacerbated CIA.
Compared to wild-type animals both the incidence and severity of arthritis were markedly reduced and joint histology showed milder inflammation. Collagen-specific IgG2a levels were lower than that of wild-type mice.
IL exerts its proinflammatory il 17 and th17 cells through various pathways Table 1. Thus, the blockade of IL-6 in the early phase of CIA inhibits Th17 differentiation, hence suppressing disease progression [ 55 ]. IL was also found to contribute to angiogenesis, as local overexpression of IL using adenoviral vectors resulted in increased endothelial staining in the ankles of CII-immunized mice compared to controls Table 1 [ 44 ].
IL production or differentiation of IL producing cells is regulated by various cytokines and cells [ 3 ]. Intra-articular overexpression of IL-4 using adenoviral vectors resulted in reduced synovial IL mRNA levels and prevented joint damage and bone erosion in CIA by suppressing osteoclastogenesis [ 57 ].
Frontiers | The Role of IL and TH17 Cells in the Bone Catabolic Activity of PTH | Immunology
Sarkar and colleagues cocultured ILtransduced dendritic cells with splenic T cells from CII-immunized mice and found that IL production by T cells was significantly reduced when T cells were harvested during the initiation phase of the disease, but that of T cells obtained during the end phase was not altered [ 81 ].
A number of cytokines regulate CIA in a network-like il 17 and th17 cells see also Table 1: In contrast, immunization with peptide-based vaccines targeting the ILp19 subunit resulted in suppressed arthritis, but IL mRNA il 17 and th17 cells and T cell populations in the spleen were not altered [ 64 ].
Preventive treatment of these mice with anti-IL inhibits CIA, with no signs of bone destruction, neutrophil infiltration, and granulopoiesis.