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Cell Rep. 2018 Apr 17;23(3):716-724. doi: 10.1016/j.celrep.2018.03.071.

Sarm1/Myd88-5 Regulates Neuronal Intrinsic Immune Response to Traumatic Axonal Injuries.

Author information

1
Center for Life Sciences, Tsinghua University, Beijing 100084, China; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
2
Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China.
3
School of Life Sciences, Peking University, Beijing 100871, China.
4
Center for Life Sciences, Tsinghua University, Beijing 100084, China.
5
School of Life Sciences, Tsinghua University, Beijing 100084, China.
6
Center for Life Sciences, Tsinghua University, Beijing 100084, China; Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China; Beijing Key Laboratory for Immunological Research on Chronic Diseases, Beijing 100084, China. Electronic address: wenwenzeng@tsinghua.edu.cn.

Abstract

Traumatic injuries can trigger inflammatory reactions, leading to profound neuropathological consequences. However, the immune capacity of neurons, distinct from that of immune cells or glial cells, in response to traumatic insults remains to be fully characterized. In this study, we demonstrate that neurons can detect, cell autonomously, distant axonal damage, resulting in rapid production of a specific collection of cytokines and chemokines. This neuronal immune response appears spatially and temporally separated from injury-induced axon degeneration. We then identify through the genetic screen that this immune response is regulated by TIR-domain adaptor Sarm1/Myd88-5. We further show that Sarm1 functions through the downstream Jnk-c-Jun signal, and blockage of this Sarm1-Jnk-c-Jun pathway effectively abolishes the recruitment of immune cells to injury-afflicted neural tissues. We therefore uncover the key function of the Sarm1 signaling pathway, independent of its known role in axon degeneration, in the neuronal intrinsic immune response to traumatic axonal injuries.

KEYWORDS:

Sarm1; neuroinflammation; neuronal intrinsic immune response; traumatic injuries

PMID:
29669278
DOI:
10.1016/j.celrep.2018.03.071
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