Article

Stress-induced remodeling of lymphoid innervation

Norman Cousins Center for PNI, Semel Institute for Neuroscience and Human Behavior, UCLA School of Medicine, USA.
Brain Behavior and Immunity (Impact Factor: 5.89). 02/2008; 22(1):15-21. DOI: 10.1016/j.bbi.2007.06.011
Source: PubMed

ABSTRACT

Lymphoid organs have long been known to harbor neural fibers from the sympathetic division of the autonomic nervous system, but recent studies suggest a surprising degree of plasticity in the density of innervation. This review summarizes data showing that behavioral stress can increase the density of catecholaminergic neural fibers within lymphoid organs of adult primates. Stress-induced neural densification is associated with increased expression of neurotrophic factors, and functional consequences include alterations in lymph node cytokine expression and increased replication of a lymphotropic virus. The finding that behavioral stress can tonically alter lymph node neural structure suggests that behavioral factors could exert long-term regulatory influences on the initiation, maintenance, and resolution of immune responses.

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Available from: John P Capitanio
    • "For example, there is a causal link from social stress, to lymphoid tissue and immune response changes, and proliferation of SIV [Capitanio et al., 2008; Capitanio & Cole, 2015; Cole, 2008; Cole et al., 2009; Sloan et al., 2007 Sloan et al., , 2008a. Adult male rhesus macaques exposed to daily changes in social partners exhibited increased innervation of their lymphoid tissues, a blunted HPA axis response to acute stress, and a causal link to weakened glucocorticoid regulations of leukocyte activity [Cole et al., 2009; Sloan et al., 2007 Sloan et al., , 2008a Sloan et al., , 2008b. The increased innervation of lymphoid tissues has also been associated with increased SIV replication [Sloan et al., 2006 [Sloan et al., , 2008b. "
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    ABSTRACT: Macaque species, specifically rhesus (Macaca mulatta), are the most common nonhuman primates (NHPs) used in biomedical research due to their suitability as a model of high priority diseases (e.g., HIV, obesity, cognitive aging), cost effective breeding and housing compared to most other NHPs, and close evolutionary relationship to humans. With this close evolutionary relationship, however, is a shared adaptation for a socially stimulating environment, without which both their welfare and suitability as a research model are compromised. While outdoor social group housing provides the best approximation of a social environment that matches the macaque behavioral biology in the wild, this is not always possible at all facilities, where animals may be housed indoors in small groups, in pairs, or alone. Further, animals may experience many housing changes in their lifetime depending on project needs, changes in social status, management needs, or health concerns. Here, we review the evidence for the physiological and health effects of social housing changes and the potential impacts on research outcomes for studies using macaques, particularly rhesus. We situate our review in the context of increasing regulatory pressure for research facilities to both house NHPs socially and mitigate trauma from social aggression. To meet these regulatory requirements and further refine the macaque model for research, significant advances must be made in our understanding and management of rhesus macaque social housing, particularly pair-housing since it is the most common social housing configuration for macaques while on research projects. Because most NHPs are adapted for sociality, a social context is likely important for improving repeatability, reproducibility, and external validity of primate biomedical research. Am. J. Primatol. © 2016 Wiley Periodicals, Inc.
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    • " , signaling and targets of sympathetic nerves in lymphoid organs ( Felten et al . , 1985 ; Felten and Felten , 1988 ; Felten , 1991 ; Straub , 2004 ) , the effect of age ( Bellinger et al . , 1992 ; Madden et al . , 1995 , 1997 , 1998 ; Friedman and Irwin , 1997 ) and stress ( Irwin , 1994 ; Marshall and Agarwal , 2000 ; Nagatomi et al . , 2000 ; Sloan et al . , 2008 ) as well as the relevance of dysregulated sympathetic nerovus system in immune - mediated disease ( Bellinger et al . , 1992 , 2008 ; Madden et al . , 1995 ; Friedman and Irwin , 1997 ; Marshall and Agarwal , 2000 ; Frohman et al . , 2001 ; Straub et al . , 2006 ; Wrona , 2006 ; del Rey and Besedovsky , 2008 ; Benarroch , 2009 ) ."
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    ABSTRACT: Innervation of the bone marrow (BM) has been described more than one century ago, however the first in vivo evidence that sympathoadrenergic fibers have a role in hematopoiesis dates back to less than 25 years ago. Evidence has since increased showing that adrenergic nerves in the BM release noradrenaline and possibly also dopamine, which act on adrenoceptors and dopaminergic receptors (DR) expressed on hematopoietic cells and affect cell survival, proliferation, migration and engraftment ability. Remarkably, dysregulation of adrenergic fibers to the BM is associated with hematopoietic disturbances and myeloproliferative disease. Several adrenergic and dopaminergic agents are already in clinical use for non-hematological indications and with a usually favorable risk-benefit profile, and are therefore potential candidates for non-conventional modulation of hematopoiesis.
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    • "A third pathway by which adverse social conditions can induce persistent transcriptional alterations in immune cells involves up-regulation of the NGF gene that supports the growth and differentiation of the SNS nerve fibers innervating lymph nodes [29]. The resulting increase in neurotransmitter delivery to the lymph node increases throughput from the brain to the immune system and thereby induces a persistent shift in the gene regulatory program of the tissue-resident pool of cells (e.g., down-regulating Type I interferon transcription and host resistance to viral infection [29]). "
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