{"id":{"repo_id":"maynooth","oai_identifier":"oai:mural.maynoothuniversity.ie:4471"},"canonical_url":"https://search.dev.ndltd.org/etd/maynooth/oai:mural.maynoothuniversity.ie:4471","repository":{"repo_id":"maynooth","name":"National University of Ireland - Maynooth","base_url":"http://mural.maynoothuniversity.ie/cgi/oai2"},"display":{"title":"Functional Characterisation of a Novel Tir-Domain containing Protein in Immune Signalling","abstract":"Dysregulation of innate immune signalling pathways has been implicated in a host of chronic inflammatory disorders including Multiple Sclerosis, Crohn’s Disease and Rheumatoid Arthritis. As a result, it is critical that there are tight regulatory mechanisms in place to rigidly control such signalling pathways. The IL-17 family of cytokines, which comprises six members in mammals, are potent mediators of inflammation. Produced primarily by CD4+ T helper 17 (Th17) cells, they signal through IL-17 receptor family complexes and protect the host against bacterial infection. Each member of the IL-17R family is composed of an extracellular Fibronectin III-like (FnIII) domain, a single transmembrane domain and an intracellular similar expression to FGF genes (SEF)/IL-17R (SEFIR) domain, which is crucial for IL-17 signalling and is homologous to the TIR domains of Toll-Like Receptors (TLRs). Here, we describe a role for IL-17RD, also known as Sef, the remaining orphan receptor of the family, as a functional regulator of innate immune signalling. Small interfering RNAs (siRNAs) and short hairpin RNAs (shRNAs) were used to suppress endogenous expression of IL-17RD leading to enhanced activation of NF-κB and NF-κB responsive genes by TLR ligands such as Lipopolysaccharide (LPS) and poyinosinic:polycytidylic acid (Poly I:C). We demonstrate that IL-17RD can differentially regulate the various pathways employed by IL-17A. Neutrophil recruitment, in response to in vivo administration of IL-17A, is abolished in IL-17RD-deficient mice, correlating with reduced IL-17A-induced activation of p38 MAPK and expression of the neutrophil chemokine MIP-2. In contrast, IL-17RD deficiency results in enhanced IL-17A-induced activation of NF-κB and IL-6 and KC expression. IL-17RD disrupts the interaction of Act1 and TRAF6 causing differential regulation of NF-κB and p38 MAPK signalling pathways.","abstract_html":"Dysregulation of innate immune signalling pathways has been implicated in a host of chronic inflammatory disorders including Multiple Sclerosis, Crohn’s Disease and Rheumatoid Arthritis. As a result, it is critical that there are tight regulatory mechanisms in place to rigidly control such signalling pathways. The IL-17 family of cytokines, which comprises six members in mammals, are potent mediators of inflammation. Produced primarily by CD4+ T helper 17 (Th17) cells, they signal through IL-17 receptor family complexes and protect the host against bacterial infection. Each member of the IL-17R family is composed of an extracellular Fibronectin III-like (FnIII) domain, a single transmembrane domain and an intracellular similar expression to FGF genes (SEF)/IL-17R (SEFIR) domain, which is crucial for IL-17 signalling and is homologous to the TIR domains of Toll-Like Receptors (TLRs). Here, we describe a role for IL-17RD, also known as Sef, the remaining orphan receptor of the family, as a functional regulator of innate immune signalling. Small interfering RNAs (siRNAs) and short hairpin RNAs (shRNAs) were used to suppress endogenous expression of IL-17RD leading to enhanced activation of NF-κB and NF-κB responsive genes by TLR ligands such as Lipopolysaccharide (LPS) and poyinosinic:polycytidylic acid (Poly I:C). We demonstrate that IL-17RD can differentially regulate the various pathways employed by IL-17A. Neutrophil recruitment, in response to in vivo administration of IL-17A, is abolished in IL-17RD-deficient mice, correlating with reduced IL-17A-induced activation of p38 MAPK and expression of the neutrophil chemokine MIP-2. In contrast, IL-17RD deficiency results in enhanced IL-17A-induced activation of NF-κB and IL-6 and KC expression. IL-17RD disrupts the interaction of Act1 and TRAF6 causing differential regulation of NF-κB and p38 MAPK signalling pathways.","abstract_has_math":false,"creators":["Horgan, Alan"],"institution":"National University of Ireland Maynooth","degree_name":null,"degree_level":"masters","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012-10","date_published":"2012-10","updated_at":"2026-07-24T03:02:41Z","subjects":["Biology"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Horgan, Alan"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2012-10"]},{"key":"dc:date.issued","label":"Date","values":["2012-10"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Biology"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["National University of Ireland Maynooth"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://mural.maynoothuniversity.ie/id/eprint/4471/"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["masters"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://mural.maynoothuniversity.ie/id/eprint/4471/1/Thesis_Alan_Horgan.pdf.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Dysregulation of innate immune signalling pathways has been implicated in a host of chronic inflammatory disorders including Multiple Sclerosis, Crohn’s Disease and Rheumatoid Arthritis. As a result, it is critical that there are tight regulatory mechanisms in place to rigidly control such signalling pathways. The IL-17 family of cytokines, which comprises six members in mammals, are potent mediators of inflammation. Produced primarily by CD4+ T helper 17 (Th17) cells, they signal through IL-17 receptor family complexes and protect the host against bacterial infection. Each member of the IL-17R family is composed of an extracellular Fibronectin III-like (FnIII) domain, a single transmembrane domain and an intracellular similar expression to FGF genes (SEF)/IL-17R (SEFIR) domain, which is crucial for IL-17 signalling and is homologous to the TIR domains of Toll-Like Receptors (TLRs). Here, we describe a role for IL-17RD, also known as Sef, the remaining orphan receptor of the family, as a functional regulator of innate immune signalling. Small interfering RNAs (siRNAs) and short hairpin RNAs (shRNAs) were used to suppress endogenous expression of IL-17RD leading to enhanced activation of NF-κB and NF-κB responsive genes by TLR ligands such as Lipopolysaccharide (LPS) and poyinosinic:polycytidylic acid (Poly I:C). We demonstrate that IL-17RD can differentially regulate the various pathways employed by IL-17A. Neutrophil recruitment, in response to in vivo administration of IL-17A, is abolished in IL-17RD-deficient mice, correlating with reduced IL-17A-induced activation of p38 MAPK and expression of the neutrophil chemokine MIP-2. In contrast, IL-17RD deficiency results in enhanced IL-17A-induced activation of NF-κB and IL-6 and KC expression. IL-17RD disrupts the interaction of Act1 and TRAF6 causing differential regulation of NF-κB and p38 MAPK signalling pathways."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Functional Characterisation of a Novel Tir-Domain containing Protein in Immune Signalling"]}]}],"canonical_facts":{"dc:creator":["Horgan, Alan"],"dc:date":["2012-10"],"dc:date.issued":["2012-10"],"dc:description.abstract":["Dysregulation of innate immune signalling pathways has been implicated in a host of chronic inflammatory disorders including Multiple Sclerosis, Crohn’s Disease and Rheumatoid Arthritis. As a result, it is critical that there are tight regulatory mechanisms in place to rigidly control such signalling pathways. The IL-17 family of cytokines, which comprises six members in mammals, are potent mediators of inflammation. Produced primarily by CD4+ T helper 17 (Th17) cells, they signal through IL-17 receptor family complexes and protect the host against bacterial infection. Each member of the IL-17R family is composed of an extracellular Fibronectin III-like (FnIII) domain, a single transmembrane domain and an intracellular similar expression to FGF genes (SEF)/IL-17R (SEFIR) domain, which is crucial for IL-17 signalling and is homologous to the TIR domains of Toll-Like Receptors (TLRs). Here, we describe a role for IL-17RD, also known as Sef, the remaining orphan receptor of the family, as a functional regulator of innate immune signalling. Small interfering RNAs (siRNAs) and short hairpin RNAs (shRNAs) were used to suppress endogenous expression of IL-17RD leading to enhanced activation of NF-κB and NF-κB responsive genes by TLR ligands such as Lipopolysaccharide (LPS) and poyinosinic:polycytidylic acid (Poly I:C). We demonstrate that IL-17RD can differentially regulate the various pathways employed by IL-17A. Neutrophil recruitment, in response to in vivo administration of IL-17A, is abolished in IL-17RD-deficient mice, correlating with reduced IL-17A-induced activation of p38 MAPK and expression of the neutrophil chemokine MIP-2. In contrast, IL-17RD deficiency results in enhanced IL-17A-induced activation of NF-κB and IL-6 and KC expression. IL-17RD disrupts the interaction of Act1 and TRAF6 causing differential regulation of NF-κB and p38 MAPK signalling pathways."],"dc:format":["application/pdf"],"dc:identifier.uri":["https://mural.maynoothuniversity.ie/id/eprint/4471/1/Thesis_Alan_Horgan.pdf.pdf"],"dc:language":["en"],"dc:publisher.department":["Biology"],"dc:publisher.institution":["National University of Ireland Maynooth"],"dc:relation.isreferencedby":["https://mural.maynoothuniversity.ie/id/eprint/4471/"],"dc:subject":["Biology"],"dc:title":["Functional Characterisation of a Novel Tir-Domain containing Protein in Immune Signalling"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["masters"]},"updated_at":"2026-07-24T03:02:41Z"}