Upregulation and pathogenic roles of CCL18-CCR8 axis in IgG4-related disease
Objectives: To determine the protein expression level, expressing cell types, and pathogenic roles of chemokine (C-C motif) ligand 18 (CCL18) and its receptor chemokine (C-C motif) receptor 8 (CCR8) in affected tissues of patients with IgG4-related disease (IgG4-RD). Methods: The protein expression...
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| Veröffentlicht in: | Modern rheumatology 2020-07, Vol.30 (4), p.729-737 |
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| creator | Tsuboi, Hiroto Iizuka-Koga, Mana Asashima, Hiromitsu Takahashi, Hiroyuki Kudo, Hanae Ono, Yuko Honda, Fumika Iizuka, Akira Segawa, Seiji Abe, Saori Yagishita, Mizuki Yokosawa, Masahiro Kondo, Yuya Moriyama, Masafumi Matsumoto, Isao Nakamura, Seiji Sumida, Takayuki |
| description | Objectives: To determine the protein expression level, expressing cell types, and pathogenic roles of chemokine (C-C motif) ligand 18 (CCL18) and its receptor chemokine (C-C motif) receptor 8 (CCR8) in affected tissues of patients with IgG4-related disease (IgG4-RD).
Methods: The protein expression levels of CCL18 in labial salivary glands (LSGs) assessed by immunofluorescence (IF) staining were compared among patients with IgG4-RD (n = 3), primary Sjögren's syndrome (pSS; n = 4), and control subjects (n = 5). CCL18 expression levels in macrophages, CD11c
+
cells, B cells, and plasmacytes in LSGs were examined by double IF staining. The protein expression levels of CCR8 and expressing cells (T, B cells, and plasmacytes) in LSGs were also compared among patients with IgG4-RD, pSS, and control subjects by double IF staining. The effects of the CCL18-CCR8 axis on total IgG, IgG2, and IgG4 production by peripheral blood mononuclear cells (PBMCs) stimulated with CD40L, IL-4, IL-10, and IL-21 were examined by in vitro assays.
Results: CCL18 was specifically upregulated in LSGs of patients with IgG4-RD, compared with only a few cells in pSS patients and none of the controls. The numbers of CCL18-producing macrophages, CD11c
+
cells, and plasmacytes in LSGs were significantly higher in IgG4-RD patients than in pSS patients and control (p |
| doi_str_mv | 10.1080/14397595.2019.1632061 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmed_primary_31203743</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2270012646</sourcerecordid><originalsourceid>FETCH-LOGICAL-c456t-9d09264ff29c3f18223c6717e3ca04c77763fab9053de186e52597025bbdf6b33</originalsourceid><addsrcrecordid>eNp9kF1LwzAUhoMobk5_gpJLbzrz0STNnVJ0CgNB3HVI02RG2qYmHbp_b8c2L706h8PznhceAK4xmmNUoDucUymYZHOCsJxjTgni-ARMd_dMcCRPj_sITcBFSp8IUSYLeQ4mFBNERU6nYLnqo11vGj340EHd1bDXw0dY284bGENjEwwOluUSF1lZvhVQ__gEfQdf1os8i3YM2hrWPlmd7CU4c7pJ9uowZ2D19PhePmfL18VL-bDMTM74kMkaScJz54g01OGCEGq4wMJSo1FuhBCcOl1JxGhtccEtI0wKRFhV1Y5XlM7A7f5vH8PXxqZBtT4Z2zS6s2GTFCECITxW8BFle9TEkFK0TvXRtzpuFUZqJ1IdRaqdSHUQOeZuDhWbqrX1X-pobgTu94DvXIit_g6xqdWgt02ILurO-DTC_3b8Anoff20</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2270012646</pqid></control><display><type>article</type><title>Upregulation and pathogenic roles of CCL18-CCR8 axis in IgG4-related disease</title><source>Oxford University Press Journals All Titles (1996-Current)</source><creator>Tsuboi, Hiroto ; Iizuka-Koga, Mana ; Asashima, Hiromitsu ; Takahashi, Hiroyuki ; Kudo, Hanae ; Ono, Yuko ; Honda, Fumika ; Iizuka, Akira ; Segawa, Seiji ; Abe, Saori ; Yagishita, Mizuki ; Yokosawa, Masahiro ; Kondo, Yuya ; Moriyama, Masafumi ; Matsumoto, Isao ; Nakamura, Seiji ; Sumida, Takayuki</creator><creatorcontrib>Tsuboi, Hiroto ; Iizuka-Koga, Mana ; Asashima, Hiromitsu ; Takahashi, Hiroyuki ; Kudo, Hanae ; Ono, Yuko ; Honda, Fumika ; Iizuka, Akira ; Segawa, Seiji ; Abe, Saori ; Yagishita, Mizuki ; Yokosawa, Masahiro ; Kondo, Yuya ; Moriyama, Masafumi ; Matsumoto, Isao ; Nakamura, Seiji ; Sumida, Takayuki</creatorcontrib><description>Objectives: To determine the protein expression level, expressing cell types, and pathogenic roles of chemokine (C-C motif) ligand 18 (CCL18) and its receptor chemokine (C-C motif) receptor 8 (CCR8) in affected tissues of patients with IgG4-related disease (IgG4-RD).
Methods: The protein expression levels of CCL18 in labial salivary glands (LSGs) assessed by immunofluorescence (IF) staining were compared among patients with IgG4-RD (n = 3), primary Sjögren's syndrome (pSS; n = 4), and control subjects (n = 5). CCL18 expression levels in macrophages, CD11c
+
cells, B cells, and plasmacytes in LSGs were examined by double IF staining. The protein expression levels of CCR8 and expressing cells (T, B cells, and plasmacytes) in LSGs were also compared among patients with IgG4-RD, pSS, and control subjects by double IF staining. The effects of the CCL18-CCR8 axis on total IgG, IgG2, and IgG4 production by peripheral blood mononuclear cells (PBMCs) stimulated with CD40L, IL-4, IL-10, and IL-21 were examined by in vitro assays.
Results: CCL18 was specifically upregulated in LSGs of patients with IgG4-RD, compared with only a few cells in pSS patients and none of the controls. The numbers of CCL18-producing macrophages, CD11c
+
cells, and plasmacytes in LSGs were significantly higher in IgG4-RD patients than in pSS patients and control (p < .05, each). Many T and B cells and some plasmacytes expressed CCR8 in LSGs of IgG4-RD and pSS patients. CCL18 specifically enhanced IgG4 production by stimulated PBMCs.
Conclusion: CCL18-CCR8 axis was upregulated in LSGs of patients with IgG4-RD, suggesting possible roles of this axis in the pathogenesis of IgG4-RD.
Key messages
The CCL18-CCR8 axis in labial salivary glands (LSGs) and lacrimal glands of IgG4-RD patients was specifically upregulated compared with primary Sjögren's syndrome and control subjects.
This axis might be a potentially novel therapeutic target in IgG4-RD, based on its important etiopathogenic roles, such as chemotaxis of various cells, induction of fibrosis, and enhancement of IgG4 production.</description><identifier>ISSN: 1439-7595</identifier><identifier>EISSN: 1439-7609</identifier><identifier>DOI: 10.1080/14397595.2019.1632061</identifier><identifier>PMID: 31203743</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>chemokine (C-C motif) ligand 18 ; chemokine (C-C motif) receptor 8 ; IgG4-related disease ; labial salivary glands ; Sjögren's syndrome</subject><ispartof>Modern rheumatology, 2020-07, Vol.30 (4), p.729-737</ispartof><rights>2019 Japan College of Rheumatology 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-9d09264ff29c3f18223c6717e3ca04c77763fab9053de186e52597025bbdf6b33</citedby><cites>FETCH-LOGICAL-c456t-9d09264ff29c3f18223c6717e3ca04c77763fab9053de186e52597025bbdf6b33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31203743$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tsuboi, Hiroto</creatorcontrib><creatorcontrib>Iizuka-Koga, Mana</creatorcontrib><creatorcontrib>Asashima, Hiromitsu</creatorcontrib><creatorcontrib>Takahashi, Hiroyuki</creatorcontrib><creatorcontrib>Kudo, Hanae</creatorcontrib><creatorcontrib>Ono, Yuko</creatorcontrib><creatorcontrib>Honda, Fumika</creatorcontrib><creatorcontrib>Iizuka, Akira</creatorcontrib><creatorcontrib>Segawa, Seiji</creatorcontrib><creatorcontrib>Abe, Saori</creatorcontrib><creatorcontrib>Yagishita, Mizuki</creatorcontrib><creatorcontrib>Yokosawa, Masahiro</creatorcontrib><creatorcontrib>Kondo, Yuya</creatorcontrib><creatorcontrib>Moriyama, Masafumi</creatorcontrib><creatorcontrib>Matsumoto, Isao</creatorcontrib><creatorcontrib>Nakamura, Seiji</creatorcontrib><creatorcontrib>Sumida, Takayuki</creatorcontrib><title>Upregulation and pathogenic roles of CCL18-CCR8 axis in IgG4-related disease</title><title>Modern rheumatology</title><addtitle>Mod Rheumatol</addtitle><description>Objectives: To determine the protein expression level, expressing cell types, and pathogenic roles of chemokine (C-C motif) ligand 18 (CCL18) and its receptor chemokine (C-C motif) receptor 8 (CCR8) in affected tissues of patients with IgG4-related disease (IgG4-RD).
Methods: The protein expression levels of CCL18 in labial salivary glands (LSGs) assessed by immunofluorescence (IF) staining were compared among patients with IgG4-RD (n = 3), primary Sjögren's syndrome (pSS; n = 4), and control subjects (n = 5). CCL18 expression levels in macrophages, CD11c
+
cells, B cells, and plasmacytes in LSGs were examined by double IF staining. The protein expression levels of CCR8 and expressing cells (T, B cells, and plasmacytes) in LSGs were also compared among patients with IgG4-RD, pSS, and control subjects by double IF staining. The effects of the CCL18-CCR8 axis on total IgG, IgG2, and IgG4 production by peripheral blood mononuclear cells (PBMCs) stimulated with CD40L, IL-4, IL-10, and IL-21 were examined by in vitro assays.
Results: CCL18 was specifically upregulated in LSGs of patients with IgG4-RD, compared with only a few cells in pSS patients and none of the controls. The numbers of CCL18-producing macrophages, CD11c
+
cells, and plasmacytes in LSGs were significantly higher in IgG4-RD patients than in pSS patients and control (p < .05, each). Many T and B cells and some plasmacytes expressed CCR8 in LSGs of IgG4-RD and pSS patients. CCL18 specifically enhanced IgG4 production by stimulated PBMCs.
Conclusion: CCL18-CCR8 axis was upregulated in LSGs of patients with IgG4-RD, suggesting possible roles of this axis in the pathogenesis of IgG4-RD.
Key messages
The CCL18-CCR8 axis in labial salivary glands (LSGs) and lacrimal glands of IgG4-RD patients was specifically upregulated compared with primary Sjögren's syndrome and control subjects.
This axis might be a potentially novel therapeutic target in IgG4-RD, based on its important etiopathogenic roles, such as chemotaxis of various cells, induction of fibrosis, and enhancement of IgG4 production.</description><subject>chemokine (C-C motif) ligand 18</subject><subject>chemokine (C-C motif) receptor 8</subject><subject>IgG4-related disease</subject><subject>labial salivary glands</subject><subject>Sjögren's syndrome</subject><issn>1439-7595</issn><issn>1439-7609</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kF1LwzAUhoMobk5_gpJLbzrz0STNnVJ0CgNB3HVI02RG2qYmHbp_b8c2L706h8PznhceAK4xmmNUoDucUymYZHOCsJxjTgni-ARMd_dMcCRPj_sITcBFSp8IUSYLeQ4mFBNERU6nYLnqo11vGj340EHd1bDXw0dY284bGENjEwwOluUSF1lZvhVQ__gEfQdf1os8i3YM2hrWPlmd7CU4c7pJ9uowZ2D19PhePmfL18VL-bDMTM74kMkaScJz54g01OGCEGq4wMJSo1FuhBCcOl1JxGhtccEtI0wKRFhV1Y5XlM7A7f5vH8PXxqZBtT4Z2zS6s2GTFCECITxW8BFle9TEkFK0TvXRtzpuFUZqJ1IdRaqdSHUQOeZuDhWbqrX1X-pobgTu94DvXIit_g6xqdWgt02ILurO-DTC_3b8Anoff20</recordid><startdate>20200703</startdate><enddate>20200703</enddate><creator>Tsuboi, Hiroto</creator><creator>Iizuka-Koga, Mana</creator><creator>Asashima, Hiromitsu</creator><creator>Takahashi, Hiroyuki</creator><creator>Kudo, Hanae</creator><creator>Ono, Yuko</creator><creator>Honda, Fumika</creator><creator>Iizuka, Akira</creator><creator>Segawa, Seiji</creator><creator>Abe, Saori</creator><creator>Yagishita, Mizuki</creator><creator>Yokosawa, Masahiro</creator><creator>Kondo, Yuya</creator><creator>Moriyama, Masafumi</creator><creator>Matsumoto, Isao</creator><creator>Nakamura, Seiji</creator><creator>Sumida, Takayuki</creator><general>Taylor & Francis</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20200703</creationdate><title>Upregulation and pathogenic roles of CCL18-CCR8 axis in IgG4-related disease</title><author>Tsuboi, Hiroto ; Iizuka-Koga, Mana ; Asashima, Hiromitsu ; Takahashi, Hiroyuki ; Kudo, Hanae ; Ono, Yuko ; Honda, Fumika ; Iizuka, Akira ; Segawa, Seiji ; Abe, Saori ; Yagishita, Mizuki ; Yokosawa, Masahiro ; Kondo, Yuya ; Moriyama, Masafumi ; Matsumoto, Isao ; Nakamura, Seiji ; Sumida, Takayuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-9d09264ff29c3f18223c6717e3ca04c77763fab9053de186e52597025bbdf6b33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>chemokine (C-C motif) ligand 18</topic><topic>chemokine (C-C motif) receptor 8</topic><topic>IgG4-related disease</topic><topic>labial salivary glands</topic><topic>Sjögren's syndrome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tsuboi, Hiroto</creatorcontrib><creatorcontrib>Iizuka-Koga, Mana</creatorcontrib><creatorcontrib>Asashima, Hiromitsu</creatorcontrib><creatorcontrib>Takahashi, Hiroyuki</creatorcontrib><creatorcontrib>Kudo, Hanae</creatorcontrib><creatorcontrib>Ono, Yuko</creatorcontrib><creatorcontrib>Honda, Fumika</creatorcontrib><creatorcontrib>Iizuka, Akira</creatorcontrib><creatorcontrib>Segawa, Seiji</creatorcontrib><creatorcontrib>Abe, Saori</creatorcontrib><creatorcontrib>Yagishita, Mizuki</creatorcontrib><creatorcontrib>Yokosawa, Masahiro</creatorcontrib><creatorcontrib>Kondo, Yuya</creatorcontrib><creatorcontrib>Moriyama, Masafumi</creatorcontrib><creatorcontrib>Matsumoto, Isao</creatorcontrib><creatorcontrib>Nakamura, Seiji</creatorcontrib><creatorcontrib>Sumida, Takayuki</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Modern rheumatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tsuboi, Hiroto</au><au>Iizuka-Koga, Mana</au><au>Asashima, Hiromitsu</au><au>Takahashi, Hiroyuki</au><au>Kudo, Hanae</au><au>Ono, Yuko</au><au>Honda, Fumika</au><au>Iizuka, Akira</au><au>Segawa, Seiji</au><au>Abe, Saori</au><au>Yagishita, Mizuki</au><au>Yokosawa, Masahiro</au><au>Kondo, Yuya</au><au>Moriyama, Masafumi</au><au>Matsumoto, Isao</au><au>Nakamura, Seiji</au><au>Sumida, Takayuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Upregulation and pathogenic roles of CCL18-CCR8 axis in IgG4-related disease</atitle><jtitle>Modern rheumatology</jtitle><addtitle>Mod Rheumatol</addtitle><date>2020-07-03</date><risdate>2020</risdate><volume>30</volume><issue>4</issue><spage>729</spage><epage>737</epage><pages>729-737</pages><issn>1439-7595</issn><eissn>1439-7609</eissn><abstract>Objectives: To determine the protein expression level, expressing cell types, and pathogenic roles of chemokine (C-C motif) ligand 18 (CCL18) and its receptor chemokine (C-C motif) receptor 8 (CCR8) in affected tissues of patients with IgG4-related disease (IgG4-RD).
Methods: The protein expression levels of CCL18 in labial salivary glands (LSGs) assessed by immunofluorescence (IF) staining were compared among patients with IgG4-RD (n = 3), primary Sjögren's syndrome (pSS; n = 4), and control subjects (n = 5). CCL18 expression levels in macrophages, CD11c
+
cells, B cells, and plasmacytes in LSGs were examined by double IF staining. The protein expression levels of CCR8 and expressing cells (T, B cells, and plasmacytes) in LSGs were also compared among patients with IgG4-RD, pSS, and control subjects by double IF staining. The effects of the CCL18-CCR8 axis on total IgG, IgG2, and IgG4 production by peripheral blood mononuclear cells (PBMCs) stimulated with CD40L, IL-4, IL-10, and IL-21 were examined by in vitro assays.
Results: CCL18 was specifically upregulated in LSGs of patients with IgG4-RD, compared with only a few cells in pSS patients and none of the controls. The numbers of CCL18-producing macrophages, CD11c
+
cells, and plasmacytes in LSGs were significantly higher in IgG4-RD patients than in pSS patients and control (p < .05, each). Many T and B cells and some plasmacytes expressed CCR8 in LSGs of IgG4-RD and pSS patients. CCL18 specifically enhanced IgG4 production by stimulated PBMCs.
Conclusion: CCL18-CCR8 axis was upregulated in LSGs of patients with IgG4-RD, suggesting possible roles of this axis in the pathogenesis of IgG4-RD.
Key messages
The CCL18-CCR8 axis in labial salivary glands (LSGs) and lacrimal glands of IgG4-RD patients was specifically upregulated compared with primary Sjögren's syndrome and control subjects.
This axis might be a potentially novel therapeutic target in IgG4-RD, based on its important etiopathogenic roles, such as chemotaxis of various cells, induction of fibrosis, and enhancement of IgG4 production.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>31203743</pmid><doi>10.1080/14397595.2019.1632061</doi><tpages>9</tpages></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current) |
| subjects | chemokine (C-C motif) ligand 18 chemokine (C-C motif) receptor 8 IgG4-related disease labial salivary glands Sjögren's syndrome |
| title | Upregulation and pathogenic roles of CCL18-CCR8 axis in IgG4-related disease |
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