2017
DOI: 10.15252/embr.201744421
|View full text |Cite
|
Sign up to set email alerts
|

Regulatory T cells are expanded by Teriparatide treatment in humans and mediate intermittent PTH ‐induced bone anabolism in mice

Abstract: Teriparatide is a bone anabolic treatment for osteoporosis, modeled in animals by intermittent PTH (iPTH) administration. iPTH-induced bone anabolism involves CD8+ T cell production of the osteogenic Wnt ligand Wnt10b, induced via yet unknown mechanisms. Here we show that Teriparatide and iPTH cause a ~2-3-fold increase in the number of regulatory T cells (Tregs) in humans and mice. Attesting in vivo relevance, blockade of the Treg increase in mice prevents iPTH-induced CD8+ T cell Wnt10b production and bone a… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

2
58
0
3

Year Published

2018
2018
2024
2024

Publication Types

Select...
7
1

Relationship

4
4

Authors

Journals

citations
Cited by 50 publications
(63 citation statements)
references
References 77 publications
2
58
0
3
Order By: Relevance
“…These discoveries prompted a need to examine the effects of SCFAs on bone volume in mice with normal gut microbiota (Figure 3). Tregs are suppressive CD4 + T cells that reside preferentially on the endosteal surfaces of bone (121); they are capable of suppressing osteoclastogenesis (107)(108)(109) and promoting osteoblast differentiation (122,123) and are required for parathyroid hormone-stimulated (PTH-stimulated) bone formation (124). The fact that SCFAs promote the differentiation of naive CD4 + cells into Tregs (56,90,91) suggests that SCFAs and probiotics that increase the production of SCFAs, such as Lactobacillus rhamnosus GG (LGG), may act through a pathway linking SCFAs, Tregs, and bone formation.…”
Section: Effects Of Scfas On Osteoclasts and Bone Resorptionmentioning
confidence: 99%
See 1 more Smart Citation
“…These discoveries prompted a need to examine the effects of SCFAs on bone volume in mice with normal gut microbiota (Figure 3). Tregs are suppressive CD4 + T cells that reside preferentially on the endosteal surfaces of bone (121); they are capable of suppressing osteoclastogenesis (107)(108)(109) and promoting osteoblast differentiation (122,123) and are required for parathyroid hormone-stimulated (PTH-stimulated) bone formation (124). The fact that SCFAs promote the differentiation of naive CD4 + cells into Tregs (56,90,91) suggests that SCFAs and probiotics that increase the production of SCFAs, such as Lactobacillus rhamnosus GG (LGG), may act through a pathway linking SCFAs, Tregs, and bone formation.…”
Section: Effects Of Scfas On Osteoclasts and Bone Resorptionmentioning
confidence: 99%
“…BM CD8 + T cells respond to PTH and butyrate by releasing Wnt10b, while silencing of Wnt10b expression by CD8 + T cells blocks the capacity of PTH and butyrate to stimulate bone formation and increase bone volume (60,(136)(137)(138). Moreover, PTH and butyrate increase the production of Wnt10b by CD8 + T cells by expanding Tregs (60,124).…”
Section: Scfas and Pth: Mechanistic Similarities And Evolutionary Conmentioning
confidence: 99%
“…iPTH causes an approximately 2-to 3-fold increase in the number of Tregs in humans and mice, which is required for iPTH to exert its bone anabolic activity (19). Tregs are suppressive helper CD4 + T cells that play an essential role in dampening inflammation and maintaining immune tolerance (20).…”
Section: Introductionmentioning
confidence: 99%
“…Die vermutlich klinisch am stärksten wirksamen Unterschiede sind diejenigen, die den Osteoklasten stimulieren und Knochenabbau bewirken. Diese sind bei langdauernder Einwirkung weitaus gravierender, möglicherweise weil sie Sekundäreffekte über T-Zellen mit einbeziehen [3,4]. Die Generierung kürzerer Polypeptide erlaubt schon rein pharmakologisch eine verkürzte Rezeptorstimulation und damit einen osteoanabolen Stimulus mit vergleichsweise geringer Osteoklasten-Aktivierung.…”
Section: Das Parathormon-paradoxunclassified
“…Komplex kann internalisiert werden und in der Zelle weiter Signale produzieren oder in Lysosomen abgebaut werden [1] Die Prinzipien dieser Schicksalsänderung des Komplexes sind auch heute noch nur teilweise verstanden. Ein wichtiger Teil der biologischen Wirkung sowohl des Knochenabbaus als auch der anabolen Wirkung läuft über die Vermehrung/Beeinflussung spezifischer T-Zellen, die sowohl zur Produktion von RANKL als auch zur anabolen Wirkung (über wnt 10b) von PTH wesentlich beitragen[3,4].…”
unclassified