Chronic stress physically spares but functionally impairs innate-like invariant T cells

Rudak, Patrick T.; Choi, Joshua J.; Parkins, Katie M.; Summers, Kelly L.; Jackson, Dwayne N.; Foster, Paula J.; Skaro, Anton I.; Leslie, Ken; McAlister, Vivian C.; Kuchroo, Vijay K.; Inoue, Wataru; Lantz, Olivier; Haeryfar, S. M. Mansour

doi:10.1016/j.celrep.2021.108979

Cited by 32 publications

(19 citation statements)

References 99 publications

(138 reference statements)

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“…As reported, long‐term exposure of mice to CVS resulted in body weight loss and progressive reduction in sucrose preference ( Figure a), reflecting diminished responsiveness to rewards that is similar to the core symptoms of major depressive disorder in human. [ 7,41 ] Notably, we detected the elevation of serological NE levels in stressed mice (Figure 7b), together with upregulated femur and serum miR‐21 expression (Figure 7c), indicating the involvement of sympathetic activation and miR‐21 in the stress pathologies. CVS treatment also led to osteopenia (Figure 7d,e) with increased bone resorption rate (Figure 7f,g) and impaired BFR (Figure S6a,b, Supporting Information).…”

Section: Resultsmentioning

confidence: 89%

Sympathetic Neurostress Drives Osteoblastic Exosomal MiR‐21 Transfer to Disrupt Bone Homeostasis and Promote Osteopenia

Sui

Liu

et al. 2021

Small Methods

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Section: Resultsmentioning

confidence: 89%

Sympathetic Neurostress Drives Osteoblastic Exosomal MiR‐21 Transfer to Disrupt Bone Homeostasis and Promote Osteopenia

Sui

Liu

et al. 2021

Small Methods

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“…ISO injection, CVS modeling and OVX surgery with their controls were performed in mice following our previous studies. 10 , 22 , 32 , 57 …”

Section: Methodsmentioning

confidence: 99%

Targeted inhibition of osteoclastogenesis reveals the pathogenesis and therapeutics of bone loss under sympathetic neurostress

et al. 2022

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Sympathetic cues via the adrenergic signaling critically regulate bone homeostasis and contribute to neurostress-induced bone loss, but the mechanisms and therapeutics remain incompletely elucidated. Here, we reveal an osteoclastogenesis-centered functionally important osteopenic pathogenesis under sympatho-adrenergic activation with characterized microRNA response and efficient therapeutics. We discovered that osteoclastic miR-21 was tightly regulated by sympatho-adrenergic cues downstream the β2-adrenergic receptor (β2AR) signaling, critically modulated osteoclastogenesis in vivo by inhibiting programmed cell death 4 (Pdcd4), and mediated detrimental effects of both isoproterenol (ISO) and chronic variable stress (CVS) on bone. Intriguingly, without affecting osteoblastic bone formation, bone protection against ISO and CVS was sufficiently achieved by a (D-Asp8)-lipid nanoparticle-mediated targeted inhibition of osteoclastic miR-21 or by clinically relevant drugs to suppress osteoclastogenesis. Collectively, these results unravel a previously underdetermined molecular and functional paradigm that osteoclastogenesis crucially contributes to sympatho-adrenergic regulation of bone and establish multiple targeted therapeutic strategies to counteract osteopenias under stresses.

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“…Lymphocyte activation and infiltration of cancers are key components of the host’s anticancer immune response [ 124 ]. Stress increases the activation of lymphocytes and produces pro-inflammatory cytokines such as interleukin-6 (IL-6) [ 125 ]. The expression levels of norepinephrine and IL-6 in ovarian cancer tissues of stressed patients were significantly increased compared to those in non-stressed patients (matched for age and disease stage) [ 126 ].…”

Section: The Role Of the Nerve In Tumor Biologymentioning

confidence: 99%

Targeting tumor innervation: premises, promises, and challenges

Peng

Yang

et al. 2022

Cell Death Discov.

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A high intratumoral nerve density is correlated with poor survival, high metastasis, and high recurrence across multiple solid tumor types. Recent research has revealed that cancer cells release diverse neurotrophic factors and exosomes to promote tumor innervation, in addition, infiltrating nerves can also mediate multiple tumor biological processes via exosomes and neurotransmitters. In this review, through seminal studies establishing tumor innervation, we discuss the communication between peripheral nerves and tumor cells in the tumor microenvironment (TME), and revealed the nerve-tumor regulation mechanisms on oncogenic process, angiogenesis, lymphangiogenesis, and immunity. Finally, we discussed the promising directions of ‘old drugs newly used’ to target TME communication and clarified a new line to prevent tumor malignant capacity.

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Chronic stress physically spares but functionally impairs innate-like invariant T cells

Cited by 32 publications

References 99 publications

Sympathetic Neurostress Drives Osteoblastic Exosomal MiR‐21 Transfer to Disrupt Bone Homeostasis and Promote Osteopenia

Sympathetic Neurostress Drives Osteoblastic Exosomal MiR‐21 Transfer to Disrupt Bone Homeostasis and Promote Osteopenia

Targeted inhibition of osteoclastogenesis reveals the pathogenesis and therapeutics of bone loss under sympathetic neurostress

Targeting tumor innervation: premises, promises, and challenges

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