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Liu et al. Neuroimmunol Neuroinflammation 2017;4:109-16 Neuroimmunology and
DOI: 10.20517/2347-8659.2017.12
Neuroinflammation

www.nnjournal.net
Minireview Open Access

How are necroptosis, immune dysfunction,

and motoneuron death connected in

amyotrophic lateral sclerosis?

Jian-Feng Liu , Ou-Xiang Zheng , Jun-Guo Xin , Hannah H. Chen , John J. Xin 4,5
1
1
2
3
1 Institute of Criminal Science and Technology, Wenzhou Police Department, Wenzhou 325000, Zhejiang, China.
2 West China College of Public Health, Sichuan University, Chengdu 610041, Sichuan, China.
3 Department of Pathology, Loyola University Medical Center, Maywood, IL 60153, USA.
4 Research and Development Service, Hines VA Hospital, Hines, IL 60141, USA.
5 Department of Pathology, The University of Chicago Medicine, Chicago, IL 60637, USA.
Correspondence to: Dr. John J. Xin, Department of Pathology, The University of Chicago Medicine, 5841 South Maryland Avenue, Rm. TW-020A,
MC0006, Chicago, IL 60637, USA. E-mail: neuroimmune@gmail.com; jxin@bsd.uchicago.edu

How to cite this article: Liu JF, Zheng OX, Xin JG, Chen HH, Xin JJ. How are necroptosis, immune dysfunction, and motoneuron death connected
in amyotrophic lateral sclerosis? Neuroimmunol Neuroinflammation 2017;4:109-16.

Dr. John J. Xin received his MD degree from West China University of Medical Sciences, and PhD degree from
Loyola University Medical Center. He completed postdoctoral training at Loyola and Hines VA Hospital, studying
the regulation of immune responses following nerve injury and in neurodegenerative diseases. Since 2012, he has
been studying the roles of autoimmunity in human diseases, including neuroinflammatory diseases (MS and ALS),
bone marrow failure, leukemia, and transplantation, funded by Muscular Dystrophy Association and Leukemia
Research Foundation. Currently, he is working at the University of Chicago and focusing on transplant immunology
clinical service and research.
ABSTRACT

Article history: Abnormal immune response/inflammation is present in patients of amyotrophic lateral sclerosis
Received: 06-03-2017 (ALS). Autoimmune-related inflammation has been thought to be involved in the pathogenesis
Accepted: 01-06-2017 of ALS. However, how the abnormal immune responses are initiated, what specific immune
Published: 16-06-2017 cells and how these immune cells are involved in this disease have not been well understood.
This is partly owing to two facts of ALS: late diagnosis and chronic nature. The late diagnosis
Key words: makes it difficult to conclude whether the abnormal immune responses/inflammation is the
Necroptosis, cause or result of the disease. The chronic nature makes it difficult to determine the best timing
Th17, for the detection of such autoimmune responses. To resolve these two challenges for research,
nerve injury, the authors introduced motor nerve injury (facial nerve axotomy, FNA) into a pre-symptomatic
amyotrophic lateral sclerosis mouse ALS model (8-week-old SOD1 G93A mice), which induces a readily detectable immune
response in a predictable time period (3-14 days). The authors found that pre-symptomatic
SOD1 G93A mice showed a higher basal level of T cell activation and Th17 cells than WT mice,
which can be further increased by FNA. However, why these pro-inflammatory Th lymphocyte

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