IL-4 expressing cells are recruited to nerve after injury and promote regeneration

Pan, Deng; Schellhardt, Lauren; Acevedo-Cintrón, Jesús A.; Hunter, Daniel A.; Snyder‐Warwick, Alison K.; Mackinnon, Susan E.; Wood, Matthew D.

doi:10.1016/j.expneurol.2021.113909

Cited by 27 publications

(20 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The polarization of the adaptive immune response has a profound impact on neuropathology outside the eye(18-20). In spontaneous autoimmune and traumatic neuropathy models involving extraocular nerves, the different types of adaptive immune responses actively promote either neural damage or regeneration (21)(22)(23)(24). Whether this also applies to corneal neuropathy development has yet to be determined, in part due to the numerous non-immune differences between disease models discussed above.…”

Section: Introductionmentioning

confidence: 99%

An ocular Th1 immune response promotes corneal nerve damage independently of the development of corneal epitheliopathy

Vereertbrugghen

Pizzano

Sabbione

et al. 2023

Preprint

View full text Add to dashboard Cite

Proper sight is not possible without a smooth, transparent cornea, which is highly exposed to environmental threats. The abundant corneal nerves are interspersed with epithelial cells in the anterior corneal surface and are instrumental to corneal integrity and immunoregulation. Conversely, corneal neuropathy is commonly observed in some immune-mediated corneal disorders but not in others, and its pathogenesis is poorly understood. Here we hypothesized that the type of adaptive immune response may influence the development of corneal neuropathy. To test this, we first immunized OT-II mice with different adjuvants that favor T helper (Th)1 or Th2 responses. Both Th1-skewed mice (measured by interferon-γproduction) and Th2-skewed (measured by interleukin-4 production) developed comparable ocular surface inflammation and conjunctival CD4+ T cell recruitment but no appreciable corneal epithelial changes upon repeated local antigenic challenge. Th1-skewed mice showed decreased corneal mechanical sensitivity and altered corneal nerve morphology (signs of corneal neuropathy) upon antigenic challenge. However, Th2-skewed mice also developed milder corneal neuropathy immediately after immunization and independently of ocular challenge, suggestive of adjuvant-induced neurotoxicity. All these findings were confirmed in wild-type mice. To circumvent unwanted neurotoxicity, CD4+ T cells from immunized mice were adoptively transferred to T cell-deficient mice. In this setup, only Th1-transferred mice developed corneal neuropathy upon antigenic challenge. To further delineate the contribution of each profile, CD4+ T cells were polarized in vitro to either Th1, Th2, or Th17 cells and transferred to T cell-deficient mice. Upon local antigenic challenge, all groups had commensurate conjunctival CD4+ T cell recruitment and macroscopic ocular inflammation. However, none of the groups developed corneal epithelial changes and only Th1-transferred mice showed signs of corneal neuropathy. Altogether the data show that corneal nerves, as opposed to corneal epithelial cells, are sensitive to immune-driven damage mediated by Th1 CD4+ T cells in the absence of other pathogenic factors. These findings have potential therapeutic implications for ocular surface disorders.

show abstract

Section: Introductionmentioning

confidence: 99%

An ocular Th1 immune response promotes corneal nerve damage independently of the development of corneal epitheliopathy

Vereertbrugghen

Pizzano

Sabbione

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…According to the results with conditioned culture, the same effect was observed for the MHFP and IL-4 groups. Therefore, it can be preliminarily concluded that RAW was polarized toward M2 under the effect of MHFPs and an AMF, 39 and there was a synergistic effect when IL-4 was combined with MHFPs and an AMF.…”

Section: Resultsmentioning

confidence: 99%

“…For a more marked effect, we added interleukin-4 (IL-4) to facilitate the recording of our results. 39 We retained the MHFPs+ group and added three new groups: IL-4, IL-4&MHFPs-, and IL-4&MHFPs+. The polarization direction of macrophages was evaluated based on the proliferation experiment results of NE-4C cells and migration experiment results of HUVECs.…”

Section: Resultsmentioning

confidence: 99%

Mesoporous hollow Fe₃O₄ nanoparticles regulate the behavior of neuro-associated cells through induction of macrophage polarization in an alternating magnetic field

Guo

Wei

et al. 2022

J. Mater. Chem. B

View full text Add to dashboard Cite

show abstract

“…In an animal study, Salman-Ehr et al [ 32 ] demonstrated that IL-4 is expressed during the early period of wound healing, but most of this cytokine was found in tissues located near the wounds. In fact, IL-4 has anti-inflammatory properties and exerts its regenerative effects directly on damaged cells [ 33 , 34 ]. Considering the systemic pro-inflammatory state immediately after surgery and the IL-4 localized effects, a blood reduction of this interleukin concentration could be expected in the postoperative period.…”

Section: Discussionmentioning

confidence: 99%

Combined spinal and general anesthesia attenuate tumor promoting effects of surgery. An experimental animal study

Inoue

Pimenta

Camargo

et al. 2022

Annals of Medicine &Amp; Surgery

View full text Add to dashboard Cite

IL-4 expressing cells are recruited to nerve after injury and promote regeneration

Cited by 27 publications

References 30 publications

An ocular Th1 immune response promotes corneal nerve damage independently of the development of corneal epitheliopathy

An ocular Th1 immune response promotes corneal nerve damage independently of the development of corneal epitheliopathy

Mesoporous hollow Fe₃O₄ nanoparticles regulate the behavior of neuro-associated cells through induction of macrophage polarization in an alternating magnetic field

Combined spinal and general anesthesia attenuate tumor promoting effects of surgery. An experimental animal study

Contact Info

Product

Resources

About

IL-4 expressing cells are recruited to nerve after injury and promote regeneration

Cited by 27 publications

References 30 publications

An ocular Th1 immune response promotes corneal nerve damage independently of the development of corneal epitheliopathy

An ocular Th1 immune response promotes corneal nerve damage independently of the development of corneal epitheliopathy

Mesoporous hollow Fe3O4 nanoparticles regulate the behavior of neuro-associated cells through induction of macrophage polarization in an alternating magnetic field

Combined spinal and general anesthesia attenuate tumor promoting effects of surgery. An experimental animal study

Contact Info

Product

Resources

About

Mesoporous hollow Fe₃O₄ nanoparticles regulate the behavior of neuro-associated cells through induction of macrophage polarization in an alternating magnetic field