Library Subscription: Guest
Begell Digital Portal Begell Digital Library eBooks Journals References & Proceedings Research Collections
Critical Reviews™ in Immunology
IF: 1.352 5-Year IF: 3.347 SJR: 0.657 SNIP: 0.55 CiteScore™: 2.19

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Volume 39, 2019 Volume 38, 2018 Volume 37, 2017 Volume 36, 2016 Volume 35, 2015 Volume 34, 2014 Volume 33, 2013 Volume 32, 2012 Volume 31, 2011 Volume 30, 2010 Volume 29, 2009 Volume 28, 2008 Volume 27, 2007 Volume 26, 2006 Volume 25, 2005 Volume 24, 2004 Volume 23, 2003 Volume 22, 2002 Volume 21, 2001 Volume 20, 2000 Volume 19, 1999 Volume 18, 1998 Volume 17, 1997 Volume 16, 1996 Volume 15, 1995 Volume 14, 1994

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v29.i1.20
pages 43-68

Function of Neurotrophic Factors Beyond the Nervous System: Inflammation and Autoimmune Demyelination

Ralf Linker
Department of Neurology, St. Josef Hospital Bochum, Ruhr-University Bochum, 44791 Bochum, Germany
Ralf Gold
Department of Neurology, St. Josef Hospital Bochum, Ruhr-University Bochum, 44791 Bochum, Germany
Fred Luhder
Institute for Multiple Sclerosis Research, University of Göttingen and Gemeinnützige Hertie-Stiftung, Waldweg 33, 37073 Göttingen, Germany


In the nervous system, neurotrophic factors play a role during development, especially for the differentiation of neuronal and glial cells. Moreover, they promote cell survival of neurons, axons, and oligodendrocytes, as well as their precursors, in vitro and in lesional paradigms. In recent years, several functions of neurotrophic factors outside the nervous system have been described, with a special focus on the immune system as well as on models of autoimmune demyelination, such as experimental autoimmune encephalomyelitis (EAE). In the family of neurotrophins, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were investigated. NGF may influence B-cell as well as T-cell function and particularly plays a role in macrophage migration into inflamed lesions. BDNF is produced by several immune-cell subtypes in vitro and also in multiple sclerosis (MS) plaques. This observation gave rise to the concept of neuroprotective autoimmunity, implying that immune-cell infiltration in the nervous system may not only be detrimental but may also play a beneficial role, for example, through the production of neurotrophic factors. In the family of neurotrophic cytokines, ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) share some common protective roles in axons and oligodendrocytes. In EAE, endogenous CNTF targets myelin, oligodendroglial cells, and axons. In contrast, LIF exerts protective functions on oligodendrocytes in some models but is also able to interact with the immune response and may modulate T-cell, monocyte and neutrophil functions. In summary, neurotrophic factors have distinct roles in the immune system during autoimmunity and may modulate immune responses as well as the susceptibility of the target tissue.