Neuropeptide signaling through neurokinin-1 and neurokinin-2 receptors augments antigen presentation by human dendritic cells

Ohtake, Junya; Kaneumi, Shun; Tanino, Mishie; Kishikawa, Takuto; Terada, Satoshi; Sumida, Kentaro; Masuko, Kazutaka; Ohno, Yosuke; Kita, Takafumi; Iwabuchi, Sadahiro; Shinohara, Toshiya; Tanino, Yoshinori; Takemura, Tamiko; Tanaka, Shinya; Kobayashi, Hiroya; Kitamura, Hiroyuki

doi:10.1016/j.jaci.2015.06.050

Cited by 14 publications

(20 citation statements)

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“…It binds to the neurokinin receptors (NK1 and NK2) located on immune cells, such as T cells. 29 , 30 The binding of SP to its receptor results in internalization of the receptor, initiates the release of cytokines 31 and stimulates macrophages. 32 …”

Section: Overview Of the Immune Systemmentioning

confidence: 99%

Immune system involvement in specific pain conditions

2017

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Chronic pain is a significant problem worldwide and is the most common disability in the United States. It is well known that the immune system plays a critical role in the development and maintenance of many chronic pain conditions. The involvement of the immune system can be through the release of autoantibodies, in the case of rheumatoid arthritis, or via cytokines, chemokines, and other inflammatory mediators (i.e. substance P, histamine, bradykinin, tumor necrosis factor, interleukins, and prostaglandins). Immune cells, such as T cells, B cells and their antibodies, and microglia are clearly key players in immune-related pain. The purpose of this review is to briefly discuss the immune system involvement in pain and to outline how it relates to rheumatoid arthritis, osteoarthritis, fibromyalgia, complex regional pain syndrome, multiple sclerosis, and diabetic neuropathy. The immune system plays a major role in many debilitating chronic pain conditions and we believe that animal models of disease and their treatments should be more directly focused on these interactions.

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Section: Overview Of the Immune Systemmentioning

confidence: 99%

Immune system involvement in specific pain conditions

2017

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“…There is evidence that SP modulates memory T cell responses directly and also indirectly, by acting on APC [123,124]. SP doses as low as 10 -8 M were found to induce the release of IL-1β, IL-6, TNF-α, and IL-23 cytokines by human Mo in vitro [125], and SP-treated Mo were potent stimulators of IL-17-producing memory T cells [123].…”

Section: Neurogenic T Cell Immunomodulationmentioning

confidence: 99%

“…In some studies, Mo pre-activation with lipopolysaccharide was necessary for SP sensing [126]. Interestingly, agonists of TLR and type I/II IFNs were shown to enhance the expression of neurokinin receptors on Mo-derived DC, and DC exposure to antagonists of those receptors attenuated phenotypic maturation induced by TLR ligands [124]. When assessed for function, Mo-DC exposed to SP receptor antagonists had a lower capacity to activate Ag-specific Th cytokine responses [124].…”

Section: Neurogenic T Cell Immunomodulationmentioning

confidence: 99%

“…Interestingly, agonists of TLR and type I/II IFNs were shown to enhance the expression of neurokinin receptors on Mo-derived DC, and DC exposure to antagonists of those receptors attenuated phenotypic maturation induced by TLR ligands [124]. When assessed for function, Mo-DC exposed to SP receptor antagonists had a lower capacity to activate Ag-specific Th cytokine responses [124]. Thus, functional neurokinin receptors in DC might be required for an optimal T cell activation by DC.…”

Section: Neurogenic T Cell Immunomodulationmentioning

confidence: 99%

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Modulation of CD4+ T Helper Cell Memory Responses in the Human Skin

Padovan

2017

Int Arch Allergy Immunol

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Immunological memory is defined as the capacity to mount faster and more effective immune responses against antigenic challenges that have been previously encountered by the host. CD4+ T helper (Th) cells play central roles in the establishment of immunological memory as they assist the functions of other leukocytes. Th cells express polarized cytokine profiles and distinct migratory and seeding capacities, but also retain a certain functional plasticity that allows them to modulate their proliferation, activity, and homing behaviour upon need. Thus, in healthy individuals, T cell immunomodulation fulfils the task of eliciting protective immune responses where they are needed. At times, however, Th plasticity can lead to collateral tissue damage and progression to autoimmune diseases or, conversely, incapacity to reject malignant tissues and clear chronic infections. Furthermore, common immune players and molecular pathways of diseases can lead to different outcomes in different individuals. A mechanistic understanding of those pathways is therefore crucial for developing precise and curative medical interventions. Here, I focus on the skin microenvironment and comprehensively describe some of the cellular and molecular determinants of CD4+ T cell memory responses in homeostatic and pathological conditions. In discussing the cellular network orchestrating cutaneous immunity, I comprehensively describe the bidirectional interaction of skin antigen-presenting cells and mononuclear phagocytes with Th17 lymphocytes, and examine how the outcome of this interaction is influenced by endogenous skin molecules, including sodium salts and neuropeptides.

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“…The tachykinins are small peptides that are derived from peptidergic fibers and other nonneural cells such as BM stroma (10)(11)(12)(13)(14). The tachykinins can modulate immune and hematopoietic responses, mostly through substance P (SP) and neurokinin (NK)-A, with each acting antagonistically to the other (7,(15)(16)(17)(18). The Tac1 gene is alternately spliced into a-, b-, l-, and d-mRNAs (19).…”

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confidence: 99%

Neuroimmune/Hematopoietic Axis with Distinct Regulation by the High-Mobility Group Box 1 in Association with Tachykinin Peptides

Gergues

Bliss

Eljarrah

et al. 2020

The Journal of Immunology

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Hematopoiesis is tightly regulated by the bone marrow (BM) niche. The niche is robust, allowing for the return of hematopoietic homeostasis after insults such as infection. Hematopoiesis is partly regulated by soluble factors, such as neuropeptides, substance P (SP), and neurokinin A (NK-A), which mediate hematopoietic stimulation and inhibition, respectively. SP and NK-A are derived from the Tac1 gene that is alternately spliced into four variants. The hematopoietic effects of SP and NK-A are mostly mediated via BM stroma. Array analyses with 2400 genes indicated distinct changes in SP-stimulated BM stroma. Computational analyses indicated networks of genes with hematopoietic regulation. Included among these networks is the high-mobility group box 1 gene (HMGB1), a nonhistone chromatin-associated protein. Validation studies indicated that NK-A could reverse SP-mediated HMGB1 decrease. Long-term culture-initiating cell assay, with or without NK-A receptor antagonist (NK2), showed a suppressive effect of HMGB1 on hematopoietic progenitors and increase in long-term culture-initiating cell assay cells (primitive hematopoietic cells). These effects occurred partly through NK-A. NSG mice with human hematopoietic system injected with the HMGB1 antagonist glycyrrhizin verified the in vitro effects of HMGB1. Although the effects on myeloid lineage were suppressed, the results suggested a more complex effect on the lymphoid lineage. Clonogenic assay for CFU– granulocyte-monocyte suggested that HMGB1 may be required to prevent hematopoietic stem cell exhaustion to ensure immune homeostasis. In summary, this study showed how HMGB1 is linked to SP and NK-A to protect the most primitive hematopoietic cell and also to maintain immune/hematopoietic homeostasis.

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Neuropeptide signaling through neurokinin-1 and neurokinin-2 receptors augments antigen presentation by human dendritic cells

Abstract: Background: Neurotransmitters, including substance P (SP) and neurokinin A (NKA),

Cited by 14 publications

References 9 publications

Immune system involvement in specific pain conditions

Immune system involvement in specific pain conditions

Modulation of CD4+ T Helper Cell Memory Responses in the Human Skin

Neuroimmune/Hematopoietic Axis with Distinct Regulation by the High-Mobility Group Box 1 in Association with Tachykinin Peptides

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