SLURP-1, an endogenous α7 nicotinic acetylcholine receptor allosteric ligand, is expressed in CD205+ dendritic cells in human tonsils and potentiates lymphocytic cholinergic activity

Fujii, Takeshi; Horiguchi, Kotaro; Sunaga, Hiroshi; Moriwaki, Yuji; Misawa, Hidemi; Kimura, Tadashi; Tsuji, Shoutaro; Kawashima, Koichiro

doi:10.1016/j.jneuroim.2013.12.003

Cited by 33 publications

(31 citation statements)

References 47 publications

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“…Fujii et al [65] detected SLURP-1 expression in CD205 + DCs (Fig. 1A, B) residing mainly in the interfollicular zone surrounding the germinal center of human tonsils.…”

Section: Slurp-1 and The Regulation Of Immune Functionmentioning

confidence: 91%

“…Razani-Boroujerdi et al [64] reported that α7 nAChRs on T cells require functional T cell receptor (TCR)/CD3 and leukocyte-specific tyrosine kinase to mediate nicotine-induced Ca 2+ -signaling via Ca 2+ release from intracellular stores, which is insensitive to α7 nAChR antagonists such as α-BTX and MLA. However, a recent study by Fujii et al [65] showed that MLA reversed the growth attenuation elicited by PHA and abolished the PHA-induced increase of ACh synthesis in MOLT-3 cells. Given that PHA activates T cells via the TCR/CD3 complex and increases ACh synthesis through up-regulation of ChAT mRNA expression via calcineurin-mediated pathways [39,40], the results suggest that α7 nAChRs linked to TCR/CD3 are sensitive to MLA.…”

Section: Nachrsmentioning

confidence: 93%

“…2) [65]. This suggests SLURP-1 activates cholinergic transmission by potentiating ACh synthesis and its action at α7 nAChRs, thereby facilitating the functional development of T cells.…”

Section: Slurp-1 and The Regulation Of Immune Functionmentioning

confidence: 99%

“…Oloffson et al [80] suggested α7 nAChRs expressed in non-T cell bone marrow-derived immune cells, together with splenic AChproducing T cells, are necessary for normal function of the inflammatory reflex leading to modulation of TNF-α synthesis. As described above, however, α7 nAChRs on T cells also act within the inflammatory reflex by stimulating ACh synthesis and release, thereby regulating proinflammatory cytokine production by macrophages [65].…”

Section: α7 Nachrs and The Regulation Of Immune Functionmentioning

confidence: 99%

“…DCs, macrophages, B cells also express both mAChRs and nAChRs, including α7 nAChRs, and CD205 + DCs express SLURP-1 (Fig. 2) [56,65].…”

Section: α7 Nachrs and The Regulation Of Immune Functionmentioning

confidence: 99%

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Non-neuronal cholinergic system in regulation of immune function with a focus on α7 nAChRs

Kawashima

Fujii

Moriwaki

et al. 2015

International Immunopharmacology

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In 1929, Dale and Dudley described the first reported natural occurrence of acetylcholine (ACh) in an animal's body. They identified this ACh in the spleens of horses and oxen, which we now know suggests possible involvement of ACh in the regulation of lymphocyte activity and immune function. However, the source and function of splenic ACh were left unexplored for several decades. Recent studies on the source of ACh in the blood revealed ACh synthesis catalyzed by choline acetyltransferase (ChAT) in CD4(+) T cells. T and B cells, macrophages and dendritic cells (DCs) all express all five muscarinic ACh receptor subtypes (mAChRs) and several subtypes of nicotinic AChRs (nAChRs), including α7 nAChRs. Stimulation of these mAChRs and nAChRs by their respective agonists causes functional and biochemical changes in the cells. Using AChR knockout mice, we found that M(1)/M(5) mAChR signaling up-regulates IgG(1) and pro-inflammatory cytokine production, while α7 nAChR signaling has the opposite effect. These findings suggest that ACh synthesized by T cells acts in an autocrine/paracrine fashion at AChRs on various immune cells to modulate immune function. In addition, an endogenous allosteric and/or orthosteric α7 nAChR ligand, SLURP-1, facilitates functional development of T cells and increases ACh synthesis via up-regulation of ChAT mRNA expression. SLURP-1 is expressed in CD205(+) DCs residing in the tonsil in close proximity to T cells, macrophages and B cells. Collectively, these findings suggest that ACh released from T cells along with SLURP-1 regulates cytokine production by activating α7 nAChRs on various immune cells, thereby facilitating T cell development and/or differentiation, leading to immune modulation.

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“…Fujii et al [65] detected SLURP-1 expression in CD205 + DCs (Fig. 1A, B) residing mainly in the interfollicular zone surrounding the germinal center of human tonsils.…”

Section: Slurp-1 and The Regulation Of Immune Functionmentioning

confidence: 91%

Section: Nachrsmentioning

confidence: 93%

“…2) [65]. This suggests SLURP-1 activates cholinergic transmission by potentiating ACh synthesis and its action at α7 nAChRs, thereby facilitating the functional development of T cells.…”

Section: Slurp-1 and The Regulation Of Immune Functionmentioning

confidence: 99%

Section: α7 Nachrs and The Regulation Of Immune Functionmentioning

confidence: 99%

“…DCs, macrophages, B cells also express both mAChRs and nAChRs, including α7 nAChRs, and CD205 + DCs express SLURP-1 (Fig. 2) [56,65].…”

Section: α7 Nachrs and The Regulation Of Immune Functionmentioning

confidence: 99%

See 3 more Smart Citations

Non-neuronal cholinergic system in regulation of immune function with a focus on α7 nAChRs

Kawashima

Fujii

Moriwaki

et al. 2015

International Immunopharmacology

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Targeting Brain α7 Nicotinic Acetylcholine Receptors in Alzheimer’s Disease: Rationale and Current Status

2014

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Alzheimer's disease (AD) is the most common form of dementia among older persons. Pathognomonic hallmarks of the disease include the development of amyloid senile plaques and deposits of neurofibrillary tangles. These changes occur in the brain long before the clinical manifestations of AD (cognitive impairment in particular) become apparent. Nicotinic acetylcholine receptors (AChRs), particularly the α7 subtype, are highly expressed in brain regions relevant to cognitive and memory functions and involved in the processing of sensory information. There is strong evidence that implicates the participation of AChRs in AD. This review briefly introduces current strategies addressing the pathophysiologic findings (amyloid-β-peptide plaques, neurofibrillary tangles) and then focuses on more recent efforts of pharmacologic intervention in AD, specifically targeted to the α7 AChR. Whereas cholinesterase inhibitors such as donepezil, galantamine, or rivastigmine, together with the non-competitive N-methyl-D-aspartate receptor antagonist memantine are at the forefront of present-day clinical intervention for AD, new insights into AChR molecular pharmacology are bringing other drugs, directed at AChRs, to center stage. Among these are the positive allosteric modulators that selectively target α7 AChRs and are aimed at unleashing the factors that hinder agonist-mediated, α7 AChR channel activation. This calls for more detailed knowledge of the distribution, functional properties, and involvement of AChRs in various signaling cascades-together with the corresponding abnormalities in all these properties-to be able to engineer strategies in drug design and evaluate the therapeutic possibilities of new compounds targeting this class of neurotransmitter receptors.

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The secreted Ly-6/uPAR related protein-1 (SLURP1) stabilizes epithelial cell junctions and suppresses TNF-α-induced cytokine production

Campbell

Tiwari

Swamynathan

2019

Biochemical and Biophysical Research Communications

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SLURP-1, an endogenous α7 nicotinic acetylcholine receptor allosteric ligand, is expressed in CD205+ dendritic cells in human tonsils and potentiates lymphocytic cholinergic activity

Cited by 33 publications

References 47 publications

Non-neuronal cholinergic system in regulation of immune function with a focus on α7 nAChRs

Non-neuronal cholinergic system in regulation of immune function with a focus on α7 nAChRs

Targeting Brain α7 Nicotinic Acetylcholine Receptors in Alzheimer’s Disease: Rationale and Current Status

The secreted Ly-6/uPAR related protein-1 (SLURP1) stabilizes epithelial cell junctions and suppresses TNF-α-induced cytokine production

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