Reprogramming adult tendon healing using regenerative neonatal regulatory T cells

Arvind, .; Kl, Howell; Huang, Alice H.

doi:10.1101/2021.05.12.443424

Cited by 7 publications

(5 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent work has only begun to appreciate the role of T cells in the tendon 42,43 . Moreover, while a lack of B and T cells did not disrupt tendon development, 5 adoptive transfer of neonatal Tregs into adult hosts improved Achilles tendon functional recovery and polarized macrophages into an anti‐inflammatory profile 44 . Collectively, these data support an important role for T cells in the healing process and merit future work to better define the role of these cells in the healing process.…”

Section: Discussionmentioning

confidence: 99%

CCR2 is expressed by tendon resident macrophage and T cells, while CCR2 deficiency impairs tendon healing via blunted involvement of tendon‐resident and circulating monocytes/macrophages

et al. 2022

View full text Add to dashboard Cite

During tendon healing, macrophages are thought to be a key mediator of scar tissue formation, which prevents successful functional restoration of the tendon. However, macrophages are critical for successful tendon healing as they aid in wound debridement, extracellular matrix deposition, and promote fibroblast proliferation. Recent work has sought to better define the multi-faceted functions of macrophages using depletion studies, while other studies have identified a tendon resident macrophage population. To begin to delineate the functions of tendon-resident versus circulation-derived macrophages, we examined the tendon healing phenotype in Chemokine Receptor 2 (CCR2) reporter (CCR2 GFP/+ ), and knockout mice. CCR2 is a chemokine receptor primarily found on the surface of circulating bone marrow-derived monocytes, with CCR2 being an important mediator of macrophage recruitment to wound environments. Surprisingly, CCR2 GFP/+ cells were present in the tendon during adult homeostasis, and singlecell RNA sequencing identified these cells as tendon-resident macrophages and T cells. During both homeostasis and healing, CCR2 knockout resulted in a substantial decrease in CCR2 GFP+ cells and pan-macrophages. Additionally, loss of CCR2 resulted in reduced numbers of myofibroblasts and impeded functional recovery during late healing. This study highlights the heterogeneity of tendonresident and recruited immune cells and their contributions following injury, and establishes an important role for CCR2 in modulating both the adult tendon cell environment and tendon healing process.

show abstract

Section: Discussionmentioning

confidence: 99%

CCR2 is expressed by tendon resident macrophage and T cells, while CCR2 deficiency impairs tendon healing via blunted involvement of tendon‐resident and circulating monocytes/macrophages

et al. 2022

View full text Add to dashboard Cite

show abstract

“…142 In a recent article about tendon healing, Huang and colleagues marked the persistent collagen damage with CHPs in the transected and unhealed Achilles tendon from neonatal mice with regulatory T cell (Treg) ablation, suggesting that the neonatal Tregs are critical for promoting tendon regeneration. 143 Collagen denaturation has also been implicated in the resolution of organ fibrosis. The hallmark of pulmonary fibrosis, a progressive and devastating interstitial lung disorder, is the excessive deposition of ECM proteins, primarily type I collagen, by activated fibroblasts.…”

Section: Collagen Denaturationmentioning

confidence: 99%

“…The Molkentin group showed that intracardiac injection of stem cells induces the accumulation of CX3CR1 + and CCR2 + macrophages in the active remodeling region of the heart (Figure c), which can reduce fibrosis and enhance the mechanical properties of the injured area by regulating the activity of local fibroblasts . In a recent article about tendon healing, Huang and colleagues marked the persistent collagen damage with CHPs in the transected and unhealed Achilles tendon from neonatal mice with regulatory T cell (Treg) ablation, suggesting that the neonatal Tregs are critical for promoting tendon regeneration …”

Section: Biology Of Collagen Hybridizationmentioning

confidence: 99%

The Chemistry and Biology of Collagen Hybridization

Zhang

et al. 2023

J. Am. Chem. Soc.

View full text Add to dashboard Cite

Collagen provides mechanical and biological support for virtually all human tissues in the extracellular matrix (ECM). Its defining molecular structure, the triple-helix, could be damaged and denatured in disease and injuries. To probe collagen damage, the concept of collagen hybridization has been proposed, revised, and validated through a series of investigations reported as early as 1973: a collagen-mimicking peptide strand may form a hybrid triple-helix with the denatured chains of natural collagen but not the intact triple-helical collagen proteins, enabling assessment of proteolytic degradation or mechanical disruption to collagen within a tissue-of-interest. Here we describe the concept and development of collagen hybridization, summarize the decades of chemical investigations on rules underlying the collagen triple-helix folding, and discuss the growing biomedical evidence on collagen denaturation as a previously overlooked ECM signature for an array of conditions involving pathological tissue remodeling and mechanical injuries. Finally, we propose a series of emerging questions regarding the chemical and biological nature of collagen denaturation and highlight the diagnostic and therapeutic opportunities from its targeting.

show abstract

“…Recent work has only begun to appreciate the role of T cells in tendon (42,43). Moreover, while a lack of B and T cells did not disrupt tendon development (5), adoptive transfer of neonatal Tregs into adult hosts improved Achilles tendon functional recovery and polarized macrophages into an anti-inflammatory profile (44). Collectively, these data support an important role for T cells in the healing process, and merit future work to better define the role of these cells in the healing process.…”

Section: Discussionmentioning

confidence: 99%

CCR2 identifies tendon resident macrophage and T cell populations while CCR2 deficiency impedes late tendon healing

Muscat

Nichols

Gira

et al. 2022

Preprint

View full text Add to dashboard Cite

During tendon healing, macrophages are thought to be a key mediator of scar tissue formation, which prevents successful functional restoration of the tendon. However, macrophages are critical for successful tendon healing as they aid in wound debridement, extracellular matrix deposition, and promote fibroblast proliferation. Recent work has sought to better define the multi-faceted functions of macrophages using depletion studies, while other studies have identified a tendon resident macrophage population. To begin to delineate the functions of tendon-resident versus circulation-derived macrophages, we examined the tendon healing phenotype in Chemokine Receptor 2 (CCR2) reporter (CCR2GFP/+), and knockout mice. CCR2 is a chemokine receptor primarily found on the surface of circulating bone marrow derived monocytes, with CCR2 being an important mediator of macrophage recruitment to wound environments. Surprisingly, CCR2GFP/+ cells were present in the tendon during adult homeostasis, and single cell RNA sequencing identified these cells as tendon-resident macrophages and T cells. During both homeostasis and healing, CCR2 knockout resulted in a substantial decrease in CCR2GFP+ cells and pan-macrophages. Additionally, loss of CCR2 resulted in reduced numbers of myofibroblasts and impeded functional recovery during late healing. This study highlights the heterogeneity of tendon-resident and recruited immune cells and their contributions following injury, and establishes an important role for CCR2 in modulating both the adult tendon cell environment and tendon healing process.

show abstract

Reprogramming adult tendon healing using regenerative neonatal regulatory T cells

Cited by 7 publications

References 59 publications

CCR2 is expressed by tendon resident macrophage and T cells, while CCR2 deficiency impairs tendon healing via blunted involvement of tendon‐resident and circulating monocytes/macrophages

CCR2 is expressed by tendon resident macrophage and T cells, while CCR2 deficiency impairs tendon healing via blunted involvement of tendon‐resident and circulating monocytes/macrophages

The Chemistry and Biology of Collagen Hybridization

CCR2 identifies tendon resident macrophage and T cell populations while CCR2 deficiency impedes late tendon healing

Contact Info

Product

Resources

About