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IL-1 receptor-related (SIGIRR) protein, also known as TIR-8, is a member of the TLR/IL-1R family that has been extensively characterised as an inhibitor of IL-1R and TLR signalling, probably through direct interaction with these receptors, MyD88, IRAK1 or TRAF6 [67] (Figure 1). Given the important role of IL-1R and TLR signalling in the chronic inflammation observed in RA [68], a regulatory role for SIGIRR in RA is not unlikely. SIGIRR has a very restricted expression pattern, being expressed in epithelial cells, monocytes and immature dendritic cells, but not in mature macro-phages [69,70]. Recently, SIGIRR overexpression was shown to inhibit the spontaneous release of inflammatory cytokines by human RA synovial cells. This inhibitory function of SIGIRR was further confirmed in vivo, since SIGIRR-deficient mice developed a more severe disease in zymosan-induced arthritis, as well as collagen-induced arthritis mouse models [70]. It will be interesting to compare the expression of SIGIRR in RA patients with its expression in control patients, or to investigate whether the function of SIGIRR is compromised in RA patients. Because of its restricted expression pattern, SIGIRR may also be an interesting therapeutic target in RA."}

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{"project":"bionlp-st-ge-2016-uniprot","denotations":[{"id":"T16058","span":{"begin":278,"end":283},"obj":"http://www.uniprot.org/uniprot/Q9Y4K3"},{"id":"T16057","span":{"begin":262,"end":267},"obj":"http://www.uniprot.org/uniprot/Q99836"}],"namespaces":[{"prefix":"_base","uri":"http://www.uniprot.org/uniprot/"}],"text":"Single-immunoglobulin IL-1 receptor-related (SIGIRR) protein, also known as TIR-8, is a member of the TLR/IL-1R family that has been extensively characterised as an inhibitor of IL-1R and TLR signalling, probably through direct interaction with these receptors, MyD88, IRAK1 or TRAF6 [67] (Figure 1). Given the important role of IL-1R and TLR signalling in the chronic inflammation observed in RA [68], a regulatory role for SIGIRR in RA is not unlikely. SIGIRR has a very restricted expression pattern, being expressed in epithelial cells, monocytes and immature dendritic cells, but not in mature macro-phages [69,70]. Recently, SIGIRR overexpression was shown to inhibit the spontaneous release of inflammatory cytokines by human RA synovial cells. This inhibitory function of SIGIRR was further confirmed in vivo, since SIGIRR-deficient mice developed a more severe disease in zymosan-induced arthritis, as well as collagen-induced arthritis mouse models [70]. It will be interesting to compare the expression of SIGIRR in RA patients with its expression in control patients, or to investigate whether the function of SIGIRR is compromised in RA patients. Because of its restricted expression pattern, SIGIRR may also be an interesting therapeutic target in RA."}

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IL-1 receptor-related (SIGIRR) protein, also known as TIR-8, is a member of the TLR/IL-1R family that has been extensively characterised as an inhibitor of IL-1R and TLR signalling, probably through direct interaction with these receptors, MyD88, IRAK1 or TRAF6 [67] (Figure 1). Given the important role of IL-1R and TLR signalling in the chronic inflammation observed in RA [68], a regulatory role for SIGIRR in RA is not unlikely. SIGIRR has a very restricted expression pattern, being expressed in epithelial cells, monocytes and immature dendritic cells, but not in mature macro-phages [69,70]. Recently, SIGIRR overexpression was shown to inhibit the spontaneous release of inflammatory cytokines by human RA synovial cells. This inhibitory function of SIGIRR was further confirmed in vivo, since SIGIRR-deficient mice developed a more severe disease in zymosan-induced arthritis, as well as collagen-induced arthritis mouse models [70]. It will be interesting to compare the expression of SIGIRR in RA patients with its expression in control patients, or to investigate whether the function of SIGIRR is compromised in RA patients. Because of its restricted expression pattern, SIGIRR may also be an interesting therapeutic target in RA."}

{"project":"UBERON-AE","denotations":[{"id":"T15483","span":{"begin":133,"end":144},"obj":"http://purl.obolibrary.org/obo/UBERON_2000106"}],"text":"Single-immunoglobulin IL-1 receptor-related (SIGIRR) protein, also known as TIR-8, is a member of the TLR/IL-1R family that has been extensively characterised as an inhibitor of IL-1R and TLR signalling, probably through direct interaction with these receptors, MyD88, IRAK1 or TRAF6 [67] (Figure 1). Given the important role of IL-1R and TLR signalling in the chronic inflammation observed in RA [68], a regulatory role for SIGIRR in RA is not unlikely. SIGIRR has a very restricted expression pattern, being expressed in epithelial cells, monocytes and immature dendritic cells, but not in mature macro-phages [69,70]. Recently, SIGIRR overexpression was shown to inhibit the spontaneous release of inflammatory cytokines by human RA synovial cells. This inhibitory function of SIGIRR was further confirmed in vivo, since SIGIRR-deficient mice developed a more severe disease in zymosan-induced arthritis, as well as collagen-induced arthritis mouse models [70]. It will be interesting to compare the expression of SIGIRR in RA patients with its expression in control patients, or to investigate whether the function of SIGIRR is compromised in RA patients. Because of its restricted expression pattern, SIGIRR may also be an interesting therapeutic target in RA."}

{"project":"GO-BP","denotations":[{"id":"T15772","span":{"begin":369,"end":381},"obj":"http://purl.obolibrary.org/obo/GO_0006954"},{"id":"T15771","span":{"begin":343,"end":353},"obj":"http://purl.obolibrary.org/obo/GO_0023052"},{"id":"T15770","span":{"begin":192,"end":202},"obj":"http://purl.obolibrary.org/obo/GO_0023052"},{"id":"T15769","span":{"begin":329,"end":334},"obj":"http://purl.obolibrary.org/obo/GO_0004908"},{"id":"T15768","span":{"begin":178,"end":183},"obj":"http://purl.obolibrary.org/obo/GO_0004908"},{"id":"T15767","span":{"begin":106,"end":111},"obj":"http://purl.obolibrary.org/obo/GO_0004908"},{"id":"T15766","span":{"begin":22,"end":35},"obj":"http://purl.obolibrary.org/obo/GO_0004908"}],"text":"Single-immunoglobulin IL-1 receptor-related (SIGIRR) protein, also known as TIR-8, is a member of the TLR/IL-1R family that has been extensively characterised as an inhibitor of IL-1R and TLR signalling, probably through direct interaction with these receptors, MyD88, IRAK1 or TRAF6 [67] (Figure 1). Given the important role of IL-1R and TLR signalling in the chronic inflammation observed in RA [68], a regulatory role for SIGIRR in RA is not unlikely. SIGIRR has a very restricted expression pattern, being expressed in epithelial cells, monocytes and immature dendritic cells, but not in mature macro-phages [69,70]. Recently, SIGIRR overexpression was shown to inhibit the spontaneous release of inflammatory cytokines by human RA synovial cells. This inhibitory function of SIGIRR was further confirmed in vivo, since SIGIRR-deficient mice developed a more severe disease in zymosan-induced arthritis, as well as collagen-induced arthritis mouse models [70]. It will be interesting to compare the expression of SIGIRR in RA patients with its expression in control patients, or to investigate whether the function of SIGIRR is compromised in RA patients. Because of its restricted expression pattern, SIGIRR may also be an interesting therapeutic target in RA."}

{"project":"GO-MF","denotations":[{"id":"T15783","span":{"begin":329,"end":334},"obj":"http://purl.obolibrary.org/obo/GO_0004908"},{"id":"T15782","span":{"begin":178,"end":183},"obj":"http://purl.obolibrary.org/obo/GO_0004908"},{"id":"T15781","span":{"begin":106,"end":111},"obj":"http://purl.obolibrary.org/obo/GO_0004908"},{"id":"T15780","span":{"begin":22,"end":35},"obj":"http://purl.obolibrary.org/obo/GO_0004908"},{"id":"T15778","span":{"begin":22,"end":26},"obj":"http://purl.obolibrary.org/obo/GO_0005149"},{"id":"T15776","span":{"begin":7,"end":21},"obj":"http://purl.obolibrary.org/obo/GO_0003823"}],"text":"Single-immunoglobulin IL-1 receptor-related (SIGIRR) protein, also known as TIR-8, is a member of the TLR/IL-1R family that has been extensively characterised as an inhibitor of IL-1R and TLR signalling, probably through direct interaction with these receptors, MyD88, IRAK1 or TRAF6 [67] (Figure 1). Given the important role of IL-1R and TLR signalling in the chronic inflammation observed in RA [68], a regulatory role for SIGIRR in RA is not unlikely. SIGIRR has a very restricted expression pattern, being expressed in epithelial cells, monocytes and immature dendritic cells, but not in mature macro-phages [69,70]. Recently, SIGIRR overexpression was shown to inhibit the spontaneous release of inflammatory cytokines by human RA synovial cells. This inhibitory function of SIGIRR was further confirmed in vivo, since SIGIRR-deficient mice developed a more severe disease in zymosan-induced arthritis, as well as collagen-induced arthritis mouse models [70]. It will be interesting to compare the expression of SIGIRR in RA patients with its expression in control patients, or to investigate whether the function of SIGIRR is compromised in RA patients. Because of its restricted expression pattern, SIGIRR may also be an interesting therapeutic target in RA."}

{"project":"GO-CC","denotations":[{"id":"T15786","span":{"begin":745,"end":750},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T15785","span":{"begin":574,"end":579},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T15784","span":{"begin":534,"end":539},"obj":"http://purl.obolibrary.org/obo/GO_0005623"}],"text":"Single-immunoglobulin IL-1 receptor-related (SIGIRR) protein, also known as TIR-8, is a member of the TLR/IL-1R family that has been extensively characterised as an inhibitor of IL-1R and TLR signalling, probably through direct interaction with these receptors, MyD88, IRAK1 or TRAF6 [67] (Figure 1). Given the important role of IL-1R and TLR signalling in the chronic inflammation observed in RA [68], a regulatory role for SIGIRR in RA is not unlikely. SIGIRR has a very restricted expression pattern, being expressed in epithelial cells, monocytes and immature dendritic cells, but not in mature macro-phages [69,70]. Recently, SIGIRR overexpression was shown to inhibit the spontaneous release of inflammatory cytokines by human RA synovial cells. This inhibitory function of SIGIRR was further confirmed in vivo, since SIGIRR-deficient mice developed a more severe disease in zymosan-induced arthritis, as well as collagen-induced arthritis mouse models [70]. It will be interesting to compare the expression of SIGIRR in RA patients with its expression in control patients, or to investigate whether the function of SIGIRR is compromised in RA patients. Because of its restricted expression pattern, SIGIRR may also be an interesting therapeutic target in RA."}

{"project":"sentences","denotations":[{"id":"T15491","span":{"begin":1160,"end":1265},"obj":"Sentence"},{"id":"T15490","span":{"begin":965,"end":1159},"obj":"Sentence"},{"id":"T15489","span":{"begin":752,"end":964},"obj":"Sentence"},{"id":"T15488","span":{"begin":621,"end":751},"obj":"Sentence"},{"id":"T15487","span":{"begin":455,"end":620},"obj":"Sentence"},{"id":"T15486","span":{"begin":301,"end":454},"obj":"Sentence"},{"id":"T15485","span":{"begin":0,"end":300},"obj":"Sentence"},{"id":"T153","span":{"begin":0,"end":300},"obj":"Sentence"},{"id":"T154","span":{"begin":301,"end":454},"obj":"Sentence"},{"id":"T155","span":{"begin":455,"end":620},"obj":"Sentence"},{"id":"T156","span":{"begin":621,"end":751},"obj":"Sentence"},{"id":"T157","span":{"begin":752,"end":964},"obj":"Sentence"},{"id":"T158","span":{"begin":965,"end":1159},"obj":"Sentence"},{"id":"T159","span":{"begin":1160,"end":1265},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Single-immunoglobulin IL-1 receptor-related (SIGIRR) protein, also known as TIR-8, is a member of the TLR/IL-1R family that has been extensively characterised as an inhibitor of IL-1R and TLR signalling, probably through direct interaction with these receptors, MyD88, IRAK1 or TRAF6 [67] (Figure 1). Given the important role of IL-1R and TLR signalling in the chronic inflammation observed in RA [68], a regulatory role for SIGIRR in RA is not unlikely. SIGIRR has a very restricted expression pattern, being expressed in epithelial cells, monocytes and immature dendritic cells, but not in mature macro-phages [69,70]. Recently, SIGIRR overexpression was shown to inhibit the spontaneous release of inflammatory cytokines by human RA synovial cells. This inhibitory function of SIGIRR was further confirmed in vivo, since SIGIRR-deficient mice developed a more severe disease in zymosan-induced arthritis, as well as collagen-induced arthritis mouse models [70]. It will be interesting to compare the expression of SIGIRR in RA patients with its expression in control patients, or to investigate whether the function of SIGIRR is compromised in RA patients. Because of its restricted expression pattern, SIGIRR may also be an interesting therapeutic target in RA."}

{"project":"ICD10","denotations":[{"id":"T15774","span":{"begin":936,"end":945},"obj":"http://purl.bioontology.org/ontology/ICD10/M13.9"},{"id":"T15773","span":{"begin":897,"end":906},"obj":"http://purl.bioontology.org/ontology/ICD10/M13.9"}],"text":"Single-immunoglobulin IL-1 receptor-related (SIGIRR) protein, also known as TIR-8, is a member of the TLR/IL-1R family that has been extensively characterised as an inhibitor of IL-1R and TLR signalling, probably through direct interaction with these receptors, MyD88, IRAK1 or TRAF6 [67] (Figure 1). Given the important role of IL-1R and TLR signalling in the chronic inflammation observed in RA [68], a regulatory role for SIGIRR in RA is not unlikely. SIGIRR has a very restricted expression pattern, being expressed in epithelial cells, monocytes and immature dendritic cells, but not in mature macro-phages [69,70]. Recently, SIGIRR overexpression was shown to inhibit the spontaneous release of inflammatory cytokines by human RA synovial cells. This inhibitory function of SIGIRR was further confirmed in vivo, since SIGIRR-deficient mice developed a more severe disease in zymosan-induced arthritis, as well as collagen-induced arthritis mouse models [70]. It will be interesting to compare the expression of SIGIRR in RA patients with its expression in control patients, or to investigate whether the function of SIGIRR is compromised in RA patients. Because of its restricted expression pattern, SIGIRR may also be an interesting therapeutic target in RA."}

{"project":"simple1","denotations":[{"id":"T15829","span":{"begin":1206,"end":1212},"obj":"Protein"},{"id":"T15828","span":{"begin":1122,"end":1128},"obj":"Protein"},{"id":"T15827","span":{"begin":1017,"end":1023},"obj":"Protein"},{"id":"T15826","span":{"begin":824,"end":830},"obj":"Protein"},{"id":"T15825","span":{"begin":780,"end":786},"obj":"Protein"},{"id":"T15824","span":{"begin":631,"end":637},"obj":"Protein"},{"id":"T15823","span":{"begin":455,"end":461},"obj":"Protein"},{"id":"T15822","span":{"begin":425,"end":431},"obj":"Protein"},{"id":"T15821","span":{"begin":329,"end":334},"obj":"Protein"},{"id":"T15820","span":{"begin":278,"end":283},"obj":"Protein"},{"id":"T15819","span":{"begin":269,"end":274},"obj":"Protein"},{"id":"T15818","span":{"begin":262,"end":267},"obj":"Protein"},{"id":"T15817","span":{"begin":178,"end":183},"obj":"Protein"},{"id":"T15816","span":{"begin":76,"end":81},"obj":"Protein"},{"id":"T15815","span":{"begin":45,"end":51},"obj":"Protein"},{"id":"T15814","span":{"begin":0,"end":43},"obj":"Protein"}],"text":"Single-immunoglobulin IL-1 receptor-related (SIGIRR) protein, also known as TIR-8, is a member of the TLR/IL-1R family that has been extensively characterised as an inhibitor of IL-1R and TLR signalling, probably through direct interaction with these receptors, MyD88, IRAK1 or TRAF6 [67] (Figure 1). Given the important role of IL-1R and TLR signalling in the chronic inflammation observed in RA [68], a regulatory role for SIGIRR in RA is not unlikely. SIGIRR has a very restricted expression pattern, being expressed in epithelial cells, monocytes and immature dendritic cells, but not in mature macro-phages [69,70]. Recently, SIGIRR overexpression was shown to inhibit the spontaneous release of inflammatory cytokines by human RA synovial cells. This inhibitory function of SIGIRR was further confirmed in vivo, since SIGIRR-deficient mice developed a more severe disease in zymosan-induced arthritis, as well as collagen-induced arthritis mouse models [70]. It will be interesting to compare the expression of SIGIRR in RA patients with its expression in control patients, or to investigate whether the function of SIGIRR is compromised in RA patients. Because of its restricted expression pattern, SIGIRR may also be an interesting therapeutic target in RA."}

{"project":"BioNLP16_DUT","denotations":[{"id":"T16200","span":{"begin":1186,"end":1196},"obj":"Gene_expression"},{"id":"T16199","span":{"begin":1252,"end":1258},"obj":"Regulation"},{"id":"T16198","span":{"begin":1003,"end":1013},"obj":"Gene_expression"},{"id":"T16197","span":{"begin":831,"end":840},"obj":"Negative_regulation"},{"id":"T16196","span":{"begin":638,"end":652},"obj":"Positive_regulation"},{"id":"T16195","span":{"begin":638,"end":652},"obj":"Gene_expression"},{"id":"T16194","span":{"begin":510,"end":519},"obj":"Gene_expression"},{"id":"T16193","span":{"begin":228,"end":239},"obj":"Binding"},{"id":"T16192","span":{"begin":165,"end":174},"obj":"Negative_regulation"},{"id":"T16191","span":{"begin":1206,"end":1212},"obj":"Protein"},{"id":"T16190","span":{"begin":1122,"end":1128},"obj":"Protein"},{"id":"T16189","span":{"begin":1017,"end":1023},"obj":"Protein"},{"id":"T16188","span":{"begin":824,"end":830},"obj":"Protein"},{"id":"T16187","span":{"begin":780,"end":786},"obj":"Protein"},{"id":"T16186","span":{"begin":631,"end":637},"obj":"Protein"},{"id":"T16185","span":{"begin":455,"end":461},"obj":"Protein"},{"id":"T16184","span":{"begin":329,"end":334},"obj":"Protein"},{"id":"T16183","span":{"begin":425,"end":431},"obj":"Protein"},{"id":"T16182","span":{"begin":278,"end":283},"obj":"Protein"},{"id":"T16181","span":{"begin":269,"end":274},"obj":"Protein"},{"id":"T16180","span":{"begin":262,"end":267},"obj":"Protein"},{"id":"T16179","span":{"begin":178,"end":183},"obj":"Protein"},{"id":"T16178","span":{"begin":76,"end":81},"obj":"Protein"},{"id":"T16177","span":{"begin":45,"end":51},"obj":"Protein"},{"id":"T16176","span":{"begin":0,"end":43},"obj":"Protein"}],"relations":[{"id":"R10719","pred":"themeOf","subj":"T16176","obj":"T16192"},{"id":"R10720","pred":"themeOf","subj":"T16176","obj":"T16193"},{"id":"R10721","pred":"themeOf","subj":"T16177","obj":"T16192"},{"id":"R10722","pred":"themeOf","subj":"T16177","obj":"T16193"},{"id":"R10723","pred":"themeOf","subj":"T16178","obj":"T16192"},{"id":"R10724","pred":"themeOf","subj":"T16178","obj":"T16193"},{"id":"R10725","pred":"themeOf","subj":"T16179","obj":"T16192"},{"id":"R10726","pred":"themeOf","subj":"T16181","obj":"T16192"},{"id":"R10727","pred":"themeOf","subj":"T16181","obj":"T16193"},{"id":"R10728","pred":"themeOf","subj":"T16185","obj":"T16194"},{"id":"R10729","pred":"themeOf","subj":"T16186","obj":"T16195"},{"id":"R10730","pred":"themeOf","subj":"T16188","obj":"T16197"},{"id":"R10731","pred":"themeOf","subj":"T16189","obj":"T16198"},{"id":"R10732","pred":"themeOf","subj":"T16191","obj":"T16199"},{"id":"R10733","pred":"themeOf","subj":"T16191","obj":"T16200"},{"id":"R10734","pred":"themeOf","subj":"T16195","obj":"T16196"}],"text":"Single-immunoglobulin IL-1 receptor-related (SIGIRR) protein, also known as TIR-8, is a member of the TLR/IL-1R family that has been extensively characterised as an inhibitor of IL-1R and TLR signalling, probably through direct interaction with these receptors, MyD88, IRAK1 or TRAF6 [67] (Figure 1). Given the important role of IL-1R and TLR signalling in the chronic inflammation observed in RA [68], a regulatory role for SIGIRR in RA is not unlikely. SIGIRR has a very restricted expression pattern, being expressed in epithelial cells, monocytes and immature dendritic cells, but not in mature macro-phages [69,70]. Recently, SIGIRR overexpression was shown to inhibit the spontaneous release of inflammatory cytokines by human RA synovial cells. This inhibitory function of SIGIRR was further confirmed in vivo, since SIGIRR-deficient mice developed a more severe disease in zymosan-induced arthritis, as well as collagen-induced arthritis mouse models [70]. It will be interesting to compare the expression of SIGIRR in RA patients with its expression in control patients, or to investigate whether the function of SIGIRR is compromised in RA patients. Because of its restricted expression pattern, SIGIRR may also be an interesting therapeutic target in RA."}

{"project":"BioNLP16_Messiy","denotations":[{"id":"T16083","span":{"begin":1186,"end":1196},"obj":"Gene_expression"},{"id":"T16082","span":{"begin":1252,"end":1258},"obj":"Regulation"},{"id":"T16081","span":{"begin":1003,"end":1013},"obj":"Gene_expression"},{"id":"T16080","span":{"begin":831,"end":840},"obj":"Negative_regulation"},{"id":"T16079","span":{"begin":638,"end":652},"obj":"Positive_regulation"},{"id":"T16078","span":{"begin":510,"end":519},"obj":"Gene_expression"},{"id":"T16077","span":{"begin":165,"end":174},"obj":"Negative_regulation"},{"id":"T16076","span":{"begin":228,"end":239},"obj":"Binding"},{"id":"T16075","span":{"begin":1206,"end":1212},"obj":"Protein"},{"id":"T16074","span":{"begin":1122,"end":1128},"obj":"Protein"},{"id":"T16073","span":{"begin":1017,"end":1023},"obj":"Protein"},{"id":"T16072","span":{"begin":824,"end":830},"obj":"Protein"},{"id":"T16064","span":{"begin":262,"end":267},"obj":"Protein"},{"id":"T16063","span":{"begin":178,"end":183},"obj":"Protein"},{"id":"T16062","span":{"begin":76,"end":81},"obj":"Protein"},{"id":"T16061","span":{"begin":45,"end":51},"obj":"Protein"},{"id":"T16060","span":{"begin":0,"end":43},"obj":"Protein"},{"id":"T16071","span":{"begin":780,"end":786},"obj":"Protein"},{"id":"T16070","span":{"begin":631,"end":637},"obj":"Protein"},{"id":"T16069","span":{"begin":455,"end":461},"obj":"Protein"},{"id":"T16068","span":{"begin":329,"end":334},"obj":"Protein"},{"id":"T16067","span":{"begin":425,"end":431},"obj":"Protein"},{"id":"T16066","span":{"begin":278,"end":283},"obj":"Protein"},{"id":"T16065","span":{"begin":269,"end":274},"obj":"Protein"}],"relations":[{"id":"R10665","pred":"themeOf","subj":"T16060","obj":"T16076"},{"id":"R10666","pred":"themeOf","subj":"T16061","obj":"T16076"},{"id":"R10667","pred":"themeOf","subj":"T16062","obj":"T16076"},{"id":"R10668","pred":"themeOf","subj":"T16063","obj":"T16076"},{"id":"R10669","pred":"themeOf","subj":"T16065","obj":"T16077"},{"id":"R10670","pred":"themeOf","subj":"T16065","obj":"T16076"},{"id":"R10671","pred":"themeOf","subj":"T16069","obj":"T16078"},{"id":"R10672","pred":"themeOf","subj":"T16070","obj":"T16079"},{"id":"R10673","pred":"themeOf","subj":"T16072","obj":"T16080"},{"id":"R10674","pred":"themeOf","subj":"T16073","obj":"T16081"},{"id":"R10675","pred":"themeOf","subj":"T16075","obj":"T16082"},{"id":"R10676","pred":"themeOf","subj":"T16075","obj":"T16083"}],"text":"Single-immunoglobulin IL-1 receptor-related (SIGIRR) protein, also known as TIR-8, is a member of the TLR/IL-1R family that has been extensively characterised as an inhibitor of IL-1R and TLR signalling, probably through direct interaction with these receptors, MyD88, IRAK1 or TRAF6 [67] (Figure 1). Given the important role of IL-1R and TLR signalling in the chronic inflammation observed in RA [68], a regulatory role for SIGIRR in RA is not unlikely. SIGIRR has a very restricted expression pattern, being expressed in epithelial cells, monocytes and immature dendritic cells, but not in mature macro-phages [69,70]. Recently, SIGIRR overexpression was shown to inhibit the spontaneous release of inflammatory cytokines by human RA synovial cells. This inhibitory function of SIGIRR was further confirmed in vivo, since SIGIRR-deficient mice developed a more severe disease in zymosan-induced arthritis, as well as collagen-induced arthritis mouse models [70]. It will be interesting to compare the expression of SIGIRR in RA patients with its expression in control patients, or to investigate whether the function of SIGIRR is compromised in RA patients. Because of its restricted expression pattern, SIGIRR may also be an interesting therapeutic target in RA."}

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