Presence and activation of pro-inflammatory macrophages are associated with CRYAB expression in vitro and after peripheral nerve injury

Journal of Neuroinflammation, 2021 · DOI: https://doi.org/10.1186/s12974-021-02108-z · Published: March 23, 2021

Simple Explanation

Following peripheral nerve injury, the body's inflammatory response plays both helpful and harmful roles. Macrophages, a type of immune cell, aid in recovery by clearing debris and supporting axon regrowth. However, prolonged inflammation can lead to negative symptoms like neuropathic pain. CRYAB, a heat shock protein, has protective functions and may regulate the immune response after nerve injury. This study investigates whether CRYAB influences the immune response following peripheral nerve injury, particularly focusing on macrophage infiltration and phenotype.

Study Duration

Not specified

Participants

Female WT and Cryab−/− mice (8-12 weeks old)

Evidence Level

Not specified

Key Findings

1
More pro-inflammatory CD16/32+ macrophages are present in the nerves of Cryab−/− mice at days 14 and 21 after sciatic nerve crush-injury compared to WT counterparts.
2
CRYAB has an immunosuppressive effect on cytokine secretion from pro-inflammatory macrophages in vitro, specifically reducing levels of IL-β, IL-6, IL-12p40, and TNF-α.
3
Myelin clearance after nerve injury is not impacted by CRYAB.

Research Summary

The study investigates the role of CRYAB, a small heat shock protein, in the immune response following peripheral nerve injury, focusing on macrophages. Results show that Cryab−/− mice exhibit a prolonged presence of pro-inflammatory macrophages in injured sciatic nerves compared to wildtype mice. In vitro experiments suggest that CRYAB suppresses pro-inflammatory cytokine production by macrophages and that it may modulate the function of pro-inflammatory-polarized macrophages by attenuating their secretion of certain pro-inflammatory cytokines.

Practical Implications

Therapeutic Potential

CRYAB may be a potential therapeutic target for curbing detrimental pro-inflammatory macrophage responses during peripheral nerve regeneration.

Pain Management

Understanding the role of CRYAB in modulating macrophage activity could lead to better strategies for managing neuropathic pain after nerve injury.

Immunomodulatory Strategies

The findings contribute to the development of immunomodulatory strategies to promote nerve regeneration while minimizing negative inflammatory effects.

Study Limitations

1
The in vitro data may not fully mirror what occurs in the nerve in vivo.
2
Tissue macrophages vary substantially based on their origin, and the peritoneal macrophages used may not reflect the proliferating endoneurial and infiltrating monocytes/macrophages present within damaged peripheral nerves.
3
LPS was used as a general macrophage stimulator, but other stimulants could produce different responses.

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