Details of a Researcher - Moriwaki, Yasuhiro

Papers - Moriwaki, Yasuhiro

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Transcriptional regulation of SLURP2, a psoriasis-associated gene, is under control of IL-22 in the skin.

Moriwaki Yasuhiro*, Takada Kiyoko, Tsuji Shoutaro, Kawashima Koichiro, Misawa Hidemi.

International Immunopharmacology 29 ( 1 ) 71 - 75 2015.02

Research paper (scientific journal), Joint Work, ISSN 1567-5769

A novel nicotinic acetylcholine (ACh) receptor (nAChR)-mediated transduction pathway, regulating keratinocyte function, has been elucidated in studies of secreted mammalian Ly6/urokinase plasminogen activator receptor-related protein (SLURP)-1 and -2. SLURPs are members of Ly6/neurotoxin superfamily (Ly6SF) of proteins containing the unique three-finger domain in their three-dimensional structure. Some endogenously expressed Ly6SF proteins (such as LYNX1, SLURP-1, and SLURP-2) modulate the function of nAChR, either as allosteric and/or orthosteric modulators, or as antagonists. Although the expression and functions of SLURP-1 and SLURP-2 in keratinocytes are well documented, the expression and the modes of action of LYNX1 in keratinocytes are unknown. Additionally, a particular hybrid transcript, LYNX1-SLURP2, which contains both LYNX1 and SLURP-2 sequences, with unknown function, has been reported. Furthermore, although SLURP2 is a gene strongly induced in psoriatic skin lesions, the mechanisms controlling SLURP2 expression are largely unknown. To better understand the function of nAChRs in keratinocytes, we investigated the expression profiles of LYNX1, LYNX1-SLURP-2, and SLURP-2 in keratinocytes under various inflammatory conditions. We found that keratinocytes express LYNX1 and SLURP2, but not LYNX1-SLURP2, at mRNA and protein levels. IL-22 treatment increased SLURP2 expression in keratinocytes, but this effect was completely abolished by IFN-γ. Furthermore, the IL-22-induced up-regulation of SLURP2 was completely suppressed by the inhibitor or siRNA for STAT3, a major transcriptional factor downstream of IL-22. These findings provide new insights into the nAChR-mediated regulatory mechanism of SLURP-2 expression in keratinocytes.

Access to Document (DOI)

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

Kawashima Koichiro, Fujii Takeshi, Moriwaki Yasuhiro, Misawa Hidemi, Horiguchi Kazuhide.

International Immunopharmacology 29 ( 1 ) 2015.02

Research paper (scientific journal), Joint Work, ISSN 1567-5769

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<inf>1</inf>/M<inf>5</inf> mAChR signaling up-regulates IgG<inf>1</inf> 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.

Access to Document (DOI)

T cells downregulate macrophage TNF production by IRAK1-mediated IL-10 expression and control innate hyperinflammation.

Inoue M, Arikawa T, Chen YH, Moriwaki Y, Price MS, Brown M, Perfect JR, Shinohara ML.

Proc Natl Acad Sci U S A 111 ( 14 ) 5295 - 5300 2014.04

Research paper (scientific journal), Joint Work, Accepted

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 T, Horiguchi K, Sunaga H, Moriwaki Y, Misawa H, Kasahara T, Tsuji S, Kawashima K.

J Neuroimmunol 267 ( 1-2 ) 43 - 49 2014.02

Research paper (scientific journal), Joint Work, Accepted

Effect of secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor- related peptide-1 (SLURP-1) on airway epithelial cells.

Narumoto O, Nikura Y, Ishii S, Morihara H, Okashiro S, Nakahari T, Nakano T, Matsumura H, Shimamoto C, Moriwaki Y, Misawa H, Yamashita N, Nagase T, Kawashima K, Yamashita N.

Biochem Biophys Res Commun. 438 ( 1 ) 175-9 2013.08

Research paper (scientific journal), Joint Work, Accepted

Localization of acetylcholine-related molecules in the retina: implication of the communication from photoreceptor to retinal pigment epithelium.

Matsumoto H, Shibasaki K, Uchigashima M, Koizumi A, Kurachi M, Moriwaki Y, Misawa H, Kawashima K, Watanabe M, Kishi S, Ishizaki Y.

PLoS One. 7 ( 8 ) e48241 2012.08

Research paper (scientific journal), Joint Work, Accepted

α-Synuclein BAC transgenic mice as a model for Parkinson's disease manifested decreased anxiety-like behavior and hyperlocomotion.

Yamakado H, Moriwaki Y, Yamasaki N, Miyakawa T, Kurisu J, Uemura K, Inoue H, Takahashi M, Takahashi R.

Neurosci Res 73 ( 2 ) 173-177 2012.06

Research paper (scientific journal), Joint Work, Accepted

Osteopontin is an alpha motor neuron marker in the mouse spinal cord.

Misawa H, Hara M, Tanabe S, Niikura M, Moriwaki Y, Okuda T.

J Neurosci Res 90 ( 4 ) 732-742 2012.04

Research paper (scientific journal), Joint Work, Accepted

Critical roles of acetylcholine and the muscarinic and nicotinic acetylcholine receptors in regulation of immune function.

Kawashima K, Fujii T, Moriwaki Y, Misawa H.

Life Sci. 91 ( 21-22 ) 1027-32 2012

Research paper (scientific journal), Joint Work, Accepted

Reconciling neuronally and non-neuronally derived acetylcholine in the regulation of immune function

Kawashima K, Fujii T, Moriwaki Y, Misawa H, Horiguchi K.

Ann N Y Acad Sci. 1261 ( 1 ) 7-17 2012

Research paper (scientific journal), Joint Work, Accepted

Critical role of intracellular osteopontin in anti-fungal innate immune responses.

Inoue M, Moriwaki Y, Arikawa T, Chen YH, Oh YJ, Oliver T, Shinohara ML.

J Immunol 186 ( 1 ) 19-23 2011.01

Research paper (scientific journal), Joint Work

The loss of PGAM5 suppresses the mitochondrial degeneration caused by inactivation of PINK1 in Drosophila.

Imai Y, Kanao T, Sawada T, Kobayashi Y, Moriwaki Y, Ishida Y, Takeda K, Ichijo H,　Lu B, Takahashi R.

PLoS Gent 6 ( 12 ) e1001229 2010.12

Research paper (scientific journal), Joint Work, Accepted

Down-regulation of secreted lymphocyte antige-6/urokinase-type plasminogen activator receptor-related peptide-1 (SLURP-1), an endogenous allosteric alpha7 nicotinic acetylcholine receptor modulator, in murine and human asthmatic conditions.

Narumoto O, Horiguchi K, Horiguchi S, Moriwaki Y, Takano-Ohmuro H, Soji S, Misawa H, Yamashita N, Nagase T, Kawashima K, Yamashita N.

Biochem Biophys Res Commun 398 ( 4 ) 713-8 2010.08

Research paper (scientific journal), Joint Work, Accepted

Acetylcholine synthesis and release in NIH3T3 cells co-expressing the high-affinity choline transporter and choline acetyltransferase.

Fujii T, Masai M, Misawa H, Okuda T, Takada-Takatori Y, Moriwaki Y, Haga T, Kawashima K.

J Neurosci Res 87 ( 13 ) 3024-32 2009.10

Research paper (scientific journal), Joint Work, Accepted

Expression of SLURP-1, an endogenous α7 nicotinic acetylcholine receptor allosteric ligand, in murine bronchial epithelial cells.

Horiguchi K, Yamashita N, Horiguchi S, Irie K, Masuda J, Takano-Ohmuro H, Himi T, Miyazawa M, Moriwaki Y, Okuda T, Misawa H, Ozaki H, Kawashima K.

J Neurosci Res 87 ( 12 ) 2740-7 2009.09

Research paper (scientific journal), Joint Work, Accepted

Primary sensory neuronal expression of SLURP-1, an endogenous nicotinic acetylcholine receptor ligand.

Moriwaki Y, Watanabe Y, Shinagawa T, Kai M, Miyazawa M, Okuda T, Kawashima K, Yabashi A, Waguri S, Misawa H.

Neurosci Res 64 ( 4 ) 403-12 2009.08

Research paper (scientific journal), Joint Work, Accepted

Aberrant trafficking of the high-affinity choline transporter in AP-3-deficient mice.

Misawa H*, Fijigaya H, Nishimura T, Moriwaki Y, Okuda T, Kawashima K, Nakata K, Ruggiero AM, Blakely RD, Nakatsu F, Ohno H.

Eur J Neurosci 27 3109-3117 2008.06

Research paper (scientific journal), Joint Work, Accepted

L347P PINK1 mutant that fails to bind to Hsp90/cdc37 chaperones is rapidly degraded in a proteasome-dependent manner.

Moriwaki Y, Kim YJ, Ido Y, Misawa H, Kawashima K, Endo S, Takahashi R.

Neurosci Res 61 ( 1 ) 43-48 2008.05

Research paper (scientific journal), Joint Work, Accepted

Production and regulation of eotaxin-2/CCL24 in a differentiated human leukemic cell line, HT93.

Yoshida N, Aizu-Yokota E, Sonoda Y, Moriwaki Y, Kishi K, Kasahara T*.

Biol Pharm Bull 30(10) 1826-1832 2007.10

Research paper (scientific journal), Joint Work, Accepted

Enhanced serum antigen-specific IgG(1) and proinflammatory cytokine production in nicotinic acetylcholine receptor a7 subunit gene knockout mice.

Fujii YX, Fujigaya H, Moriwaki Y, Misawa H, Kasahara T, Grando SA, Kawashima K*.

J Neuroimmunol 189(1-2) 69-74 2007.09

Research paper (scientific journal), Joint Work, Accepted

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