Involvement of Syk in pathology of systemic autoimmune disease

Shigeru Iwata, Kunihiro Yamaoka, Kazuhisa Nakano, Sheau Pey Wang, Kazuyoshi Saito, Yoshiya Tanaka, Hiroaki Niiro, Koichi Akashi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Biological products have proven its high efficacy on autoimmune disease such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Meanwhile, small molecular drugs have attracted attention over the years because of its availability of oral administration and cost effectiveness. Spleen tyrosine kinase (Syk) is a 72 kDa protein tyrosine kinase widely expressed on cells that are involved in the immune system and inflammation such as B cells, T cells, macrophages and synovial fibroblast. Syk is involved in intracellular signaling of the multi-chain immune receptors, including B cell receptor (BCR), ξchain of T-cell receptor (TCR), FcR and integrins, which contains the immune-receptor tyrosine-based activation motif (ITAM). Recently, Syk inhibitor fostamatinib has exerted potent therapeutic efficacy against autoimmune and allergic diseases such as rheumatoid arthritis (RA), bronchial asthma and thrombocytopenic purpura (ITP). Moreover, Syk blockade prevented the development of skin and kidney lesions in lupus-prone mice, however the mechanism of action is unclear. We have revealed that Syk-mediated BCR-signaling is prerequisite for optimal induction of toll-like receptor (TLR)L9, thereby allowing e-cient propagation of CD40- and TLR9- signaling in human B cells. These results indicate that inhibition of Syk have a potential to regulate B-cell mediated inflammatory diseases such as SLE. We here document the in vitro and in vivo effects of a Syk inhibitor for the treatment of autoimmune diseases, mainly in RA and SLE.

Original languageEnglish
Pages (from-to)56-61
Number of pages6
JournalJapanese Journal of Clinical Immunology
Volume35
Issue number1
DOIs
Publication statusPublished - 2012
Externally publishedYes

Fingerprint

Autoimmune Diseases
Pathology
B-Lymphocytes
Systemic Lupus Erythematosus
Rheumatoid Arthritis
Immunoreceptor Tyrosine-Based Activation Motif
Thrombocytopenic Purpura
Inosine Triphosphate
Toll-Like Receptors
T-Cell Antigen Receptor
Syk Kinase
Biological Products
Integrins
Protein-Tyrosine Kinases
Cost-Benefit Analysis
Oral Administration
Immune System
Asthma
Fibroblasts
Macrophages

Keywords

  • B cell
  • RA
  • SLE
  • Syk
  • TLR9
  • TRAF6

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Iwata, S., Yamaoka, K., Nakano, K., Wang, S. P., Saito, K., Tanaka, Y., ... Akashi, K. (2012). Involvement of Syk in pathology of systemic autoimmune disease. Japanese Journal of Clinical Immunology, 35(1), 56-61. https://doi.org/10.2177/jsci.35.56

Involvement of Syk in pathology of systemic autoimmune disease. / Iwata, Shigeru; Yamaoka, Kunihiro; Nakano, Kazuhisa; Wang, Sheau Pey; Saito, Kazuyoshi; Tanaka, Yoshiya; Niiro, Hiroaki; Akashi, Koichi.

In: Japanese Journal of Clinical Immunology, Vol. 35, No. 1, 2012, p. 56-61.

Research output: Contribution to journalArticle

Iwata, S, Yamaoka, K, Nakano, K, Wang, SP, Saito, K, Tanaka, Y, Niiro, H & Akashi, K 2012, 'Involvement of Syk in pathology of systemic autoimmune disease', Japanese Journal of Clinical Immunology, vol. 35, no. 1, pp. 56-61. https://doi.org/10.2177/jsci.35.56
Iwata, Shigeru ; Yamaoka, Kunihiro ; Nakano, Kazuhisa ; Wang, Sheau Pey ; Saito, Kazuyoshi ; Tanaka, Yoshiya ; Niiro, Hiroaki ; Akashi, Koichi. / Involvement of Syk in pathology of systemic autoimmune disease. In: Japanese Journal of Clinical Immunology. 2012 ; Vol. 35, No. 1. pp. 56-61.
@article{f9fe2d23f49046f5be549459c58201b1,
title = "Involvement of Syk in pathology of systemic autoimmune disease",
abstract = "Biological products have proven its high efficacy on autoimmune disease such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Meanwhile, small molecular drugs have attracted attention over the years because of its availability of oral administration and cost effectiveness. Spleen tyrosine kinase (Syk) is a 72 kDa protein tyrosine kinase widely expressed on cells that are involved in the immune system and inflammation such as B cells, T cells, macrophages and synovial fibroblast. Syk is involved in intracellular signaling of the multi-chain immune receptors, including B cell receptor (BCR), ξchain of T-cell receptor (TCR), FcR and integrins, which contains the immune-receptor tyrosine-based activation motif (ITAM). Recently, Syk inhibitor fostamatinib has exerted potent therapeutic efficacy against autoimmune and allergic diseases such as rheumatoid arthritis (RA), bronchial asthma and thrombocytopenic purpura (ITP). Moreover, Syk blockade prevented the development of skin and kidney lesions in lupus-prone mice, however the mechanism of action is unclear. We have revealed that Syk-mediated BCR-signaling is prerequisite for optimal induction of toll-like receptor (TLR)L9, thereby allowing e-cient propagation of CD40- and TLR9- signaling in human B cells. These results indicate that inhibition of Syk have a potential to regulate B-cell mediated inflammatory diseases such as SLE. We here document the in vitro and in vivo effects of a Syk inhibitor for the treatment of autoimmune diseases, mainly in RA and SLE.",
keywords = "B cell, RA, SLE, Syk, TLR9, TRAF6",
author = "Shigeru Iwata and Kunihiro Yamaoka and Kazuhisa Nakano and Wang, {Sheau Pey} and Kazuyoshi Saito and Yoshiya Tanaka and Hiroaki Niiro and Koichi Akashi",
year = "2012",
doi = "10.2177/jsci.35.56",
language = "English",
volume = "35",
pages = "56--61",
journal = "Immunological Medicine",
issn = "0911-4300",
publisher = "Taylor and Francis Ltd.",
number = "1",

}

TY - JOUR

T1 - Involvement of Syk in pathology of systemic autoimmune disease

AU - Iwata, Shigeru

AU - Yamaoka, Kunihiro

AU - Nakano, Kazuhisa

AU - Wang, Sheau Pey

AU - Saito, Kazuyoshi

AU - Tanaka, Yoshiya

AU - Niiro, Hiroaki

AU - Akashi, Koichi

PY - 2012

Y1 - 2012

N2 - Biological products have proven its high efficacy on autoimmune disease such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Meanwhile, small molecular drugs have attracted attention over the years because of its availability of oral administration and cost effectiveness. Spleen tyrosine kinase (Syk) is a 72 kDa protein tyrosine kinase widely expressed on cells that are involved in the immune system and inflammation such as B cells, T cells, macrophages and synovial fibroblast. Syk is involved in intracellular signaling of the multi-chain immune receptors, including B cell receptor (BCR), ξchain of T-cell receptor (TCR), FcR and integrins, which contains the immune-receptor tyrosine-based activation motif (ITAM). Recently, Syk inhibitor fostamatinib has exerted potent therapeutic efficacy against autoimmune and allergic diseases such as rheumatoid arthritis (RA), bronchial asthma and thrombocytopenic purpura (ITP). Moreover, Syk blockade prevented the development of skin and kidney lesions in lupus-prone mice, however the mechanism of action is unclear. We have revealed that Syk-mediated BCR-signaling is prerequisite for optimal induction of toll-like receptor (TLR)L9, thereby allowing e-cient propagation of CD40- and TLR9- signaling in human B cells. These results indicate that inhibition of Syk have a potential to regulate B-cell mediated inflammatory diseases such as SLE. We here document the in vitro and in vivo effects of a Syk inhibitor for the treatment of autoimmune diseases, mainly in RA and SLE.

AB - Biological products have proven its high efficacy on autoimmune disease such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Meanwhile, small molecular drugs have attracted attention over the years because of its availability of oral administration and cost effectiveness. Spleen tyrosine kinase (Syk) is a 72 kDa protein tyrosine kinase widely expressed on cells that are involved in the immune system and inflammation such as B cells, T cells, macrophages and synovial fibroblast. Syk is involved in intracellular signaling of the multi-chain immune receptors, including B cell receptor (BCR), ξchain of T-cell receptor (TCR), FcR and integrins, which contains the immune-receptor tyrosine-based activation motif (ITAM). Recently, Syk inhibitor fostamatinib has exerted potent therapeutic efficacy against autoimmune and allergic diseases such as rheumatoid arthritis (RA), bronchial asthma and thrombocytopenic purpura (ITP). Moreover, Syk blockade prevented the development of skin and kidney lesions in lupus-prone mice, however the mechanism of action is unclear. We have revealed that Syk-mediated BCR-signaling is prerequisite for optimal induction of toll-like receptor (TLR)L9, thereby allowing e-cient propagation of CD40- and TLR9- signaling in human B cells. These results indicate that inhibition of Syk have a potential to regulate B-cell mediated inflammatory diseases such as SLE. We here document the in vitro and in vivo effects of a Syk inhibitor for the treatment of autoimmune diseases, mainly in RA and SLE.

KW - B cell

KW - RA

KW - SLE

KW - Syk

KW - TLR9

KW - TRAF6

UR - http://www.scopus.com/inward/record.url?scp=84977559316&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84977559316&partnerID=8YFLogxK

U2 - 10.2177/jsci.35.56

DO - 10.2177/jsci.35.56

M3 - Article

AN - SCOPUS:84977559316

VL - 35

SP - 56

EP - 61

JO - Immunological Medicine

JF - Immunological Medicine

SN - 0911-4300

IS - 1

ER -