{"id":{"repo_id":"soton","oai_identifier":"oai:eprints.soton.ac.uk:196569"},"canonical_url":"https://search.dev.ndltd.org/etd/soton/oai:eprints.soton.ac.uk:196569","repository":{"repo_id":"soton","name":"University of Southampton","base_url":"https://eprints.soton.ac.uk/cgi/oai2"},"display":{"title":"Role of microRNA-155 in dendritic cells and macrophages: MiR-155 directly targets PU.1 and IL13Rα1","abstract":"In search of genes differentially expressed between M1 (pro-Th<sub>1</sub> or pro-inflammatory) and M2 (pro-Th<sub>2</sub> or pro-tolerogenic) macrophages, BIC (microRNA 155 hosting gene) was found up regulated under inflammatory conditions. MicroRNAs are non coding RNAs of ~22nt in length that inhibit gene expression upon pairing to the 3’UTR (UnTranslated Region) of target mRNAs. <i>In silico </i>analysis predicted two pro-Th<sub>2</sub> targets for miR-155: PU.1 and IL13Rα1. PU.1 is a transcription factor essential in myelopoiesis and dendritic cells (DCs) that favours a Th<sub>2</sub> profiling; moreover, PU.1 had been shown to regulate the transcription of DC-SIGN (Dendritic Cell-Specific ICAM-3 Grabbing Non-integrin 1) which is a pathogen receptor expressed in DCs controlled by Th<sub>2</sub> stimuli. IL13Rα1 is the chain receptor for the Th<sub>2</sub> cytokine IL-13, which promotes M2 differentiation. Pro Th<sub>1</sub> stimuli cause maturation of DCs, cells that orchestrate the immune response between Th<sub>1</sub> and Th<sub>2</sub> profiles; moreover, Th<sub>1</sub> stimuli cause classical (M1) macrophages activation versus an alternative (M2) one. My hypothesis was that miR-155 contributes to the pro-Th<sub>1</sub> profile by down regulating pro-Th<sub>2</sub> factors. MiR-155 was found up regulated during DC maturation and both PU.1 and IL13Rα1 were demonstrated as direct targets of miR-155. Employing a developed monocytic cell line which harbors a miR-155 transgene under the control of a Tet-On system (THP1-155 cells), both PU.1 and IL13Rα1 were shown to be down regulated following miR-155 induction in these cells. Moreover, THP1-155 cells showed that DC-SIGN transcription is regulated by miR-155 levels through PU.1 targeting, and that IL-13 signalling cascade through STAT6 transcription factor was down regulated when miR-155 was over expressed. Using Anti miR-155 transfections in DCs, miR-155 was shown to modulate not only DC-SIGN expression, but also DC pathogen binding ability. Using the same technique in macrophages, miR-155 was shown to modulate IL13Rα1 and STAT6 activation, and to regulate the expression of IL-13/STAT6 dependent genes. Therefore, miR-155 contributes to the pro-Th<sub>1</sub> profile by down regulating pro-Th<sub>2</sub> factors, acting as a pro-Th<sub>1</sub>/anti-Th<sub>2</sub> modulator in myeloid cells under inflammatory conditions.","abstract_html":"In search of genes differentially expressed between M1 (pro-Th&lt;sub&gt;1&lt;/sub&gt; or pro-inflammatory) and M2 (pro-Th&lt;sub&gt;2&lt;/sub&gt; or pro-tolerogenic) macrophages, BIC (microRNA 155 hosting gene) was found up regulated under inflammatory conditions. MicroRNAs are non coding RNAs of ~22nt in length that inhibit gene expression upon pairing to the 3’UTR (UnTranslated Region) of target mRNAs. &lt;i&gt;In silico &lt;/i&gt;analysis predicted two pro-Th&lt;sub&gt;2&lt;/sub&gt; targets for miR-155: PU.1 and IL13Rα1. PU.1 is a transcription factor essential in myelopoiesis and dendritic cells (DCs) that favours a Th&lt;sub&gt;2&lt;/sub&gt; profiling; moreover, PU.1 had been shown to regulate the transcription of DC-SIGN (Dendritic Cell-Specific ICAM-3 Grabbing Non-integrin 1) which is a pathogen receptor expressed in DCs controlled by Th&lt;sub&gt;2&lt;/sub&gt; stimuli. IL13Rα1 is the chain receptor for the Th&lt;sub&gt;2&lt;/sub&gt; cytokine IL-13, which promotes M2 differentiation. Pro Th&lt;sub&gt;1&lt;/sub&gt; stimuli cause maturation of DCs, cells that orchestrate the immune response between Th&lt;sub&gt;1&lt;/sub&gt; and Th&lt;sub&gt;2&lt;/sub&gt; profiles; moreover, Th&lt;sub&gt;1&lt;/sub&gt; stimuli cause classical (M1) macrophages activation versus an alternative (M2) one. My hypothesis was that miR-155 contributes to the pro-Th&lt;sub&gt;1&lt;/sub&gt; profile by down regulating pro-Th&lt;sub&gt;2&lt;/sub&gt; factors. MiR-155 was found up regulated during DC maturation and both PU.1 and IL13Rα1 were demonstrated as direct targets of miR-155. Employing a developed monocytic cell line which harbors a miR-155 transgene under the control of a Tet-On system (THP1-155 cells), both PU.1 and IL13Rα1 were shown to be down regulated following miR-155 induction in these cells. Moreover, THP1-155 cells showed that DC-SIGN transcription is regulated by miR-155 levels through PU.1 targeting, and that IL-13 signalling cascade through STAT6 transcription factor was down regulated when miR-155 was over expressed. Using Anti miR-155 transfections in DCs, miR-155 was shown to modulate not only DC-SIGN expression, but also DC pathogen binding ability. Using the same technique in macrophages, miR-155 was shown to modulate IL13Rα1 and STAT6 activation, and to regulate the expression of IL-13/STAT6 dependent genes. Therefore, miR-155 contributes to the pro-Th&lt;sub&gt;1&lt;/sub&gt; profile by down regulating pro-Th&lt;sub&gt;2&lt;/sub&gt; factors, acting as a pro-Th&lt;sub&gt;1&lt;/sub&gt;/anti-Th&lt;sub&gt;2&lt;/sub&gt; modulator in myeloid cells under inflammatory conditions.","abstract_has_math":false,"creators":["Martinez‐Nunez, Rocio Teresa"],"institution":"University of Southampton","degree_name":"Ph.D.","degree_level":"doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Sanchez-Elsner, Tilman"],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-10","date_published":"2010-10","updated_at":"2026-07-24T04:36:32Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Sanchez-Elsner, Tilman"]},{"key":"dc:creator","label":"Author","values":["Martinez‐Nunez, Rocio Teresa"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2010-10"]},{"key":"dc:date.issued","label":"Date","values":["2010-10"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Clinical & Experimental Sciences (pre 2018 reorg)","School of Medicine"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Southampton"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://eprints.soton.ac.uk/196569/"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Ph.D."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://eprints.soton.ac.uk/196569/1/Rocio_Teresa_Martinez-Nunez_PhD_2010.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["In search of genes differentially expressed between M1 (pro-Th<sub>1</sub> or pro-inflammatory) and M2 (pro-Th<sub>2</sub> or pro-tolerogenic) macrophages, BIC (microRNA 155 hosting gene) was found up regulated under inflammatory conditions. MicroRNAs are non coding RNAs of ~22nt in length that inhibit gene expression upon pairing to the 3’UTR (UnTranslated Region) of target mRNAs. <i>In silico </i>analysis predicted two pro-Th<sub>2</sub> targets for miR-155: PU.1 and IL13Rα1. PU.1 is a transcription factor essential in myelopoiesis and dendritic cells (DCs) that favours a Th<sub>2</sub> profiling; moreover, PU.1 had been shown to regulate the transcription of DC-SIGN (Dendritic Cell-Specific ICAM-3 Grabbing Non-integrin 1) which is a pathogen receptor expressed in DCs controlled by Th<sub>2</sub> stimuli. IL13Rα1 is the chain receptor for the Th<sub>2</sub> cytokine IL-13, which promotes M2 differentiation. Pro Th<sub>1</sub> stimuli cause maturation of DCs, cells that orchestrate the immune response between Th<sub>1</sub> and Th<sub>2</sub> profiles; moreover, Th<sub>1</sub> stimuli cause classical (M1) macrophages activation versus an alternative (M2) one. My hypothesis was that miR-155 contributes to the pro-Th<sub>1</sub> profile by down regulating pro-Th<sub>2</sub> factors. MiR-155 was found up regulated during DC maturation and both PU.1 and IL13Rα1 were demonstrated as direct targets of miR-155. Employing a developed monocytic cell line which harbors a miR-155 transgene under the control of a Tet-On system (THP1-155 cells), both PU.1 and IL13Rα1 were shown to be down regulated following miR-155 induction in these cells. Moreover, THP1-155 cells showed that DC-SIGN transcription is regulated by miR-155 levels through PU.1 targeting, and that IL-13 signalling cascade through STAT6 transcription factor was down regulated when miR-155 was over expressed. Using Anti miR-155 transfections in DCs, miR-155 was shown to modulate not only DC-SIGN expression, but also DC pathogen binding ability. Using the same technique in macrophages, miR-155 was shown to modulate IL13Rα1 and STAT6 activation, and to regulate the expression of IL-13/STAT6 dependent genes. Therefore, miR-155 contributes to the pro-Th<sub>1</sub> profile by down regulating pro-Th<sub>2</sub> factors, acting as a pro-Th<sub>1</sub>/anti-Th<sub>2</sub> modulator in myeloid cells under inflammatory conditions."]},{"key":"dc:format","label":"Dc Format","values":["text"]},{"key":"dc:title","label":"Title","values":["Role of microRNA-155 in dendritic cells and macrophages: MiR-155 directly targets PU.1 and IL13Rα1"]}]}],"canonical_facts":{"dc:contributor.advisor":["Sanchez-Elsner, Tilman"],"dc:creator":["Martinez‐Nunez, Rocio Teresa"],"dc:date":["2010-10"],"dc:date.issued":["2010-10"],"dc:description.abstract":["In search of genes differentially expressed between M1 (pro-Th<sub>1</sub> or pro-inflammatory) and M2 (pro-Th<sub>2</sub> or pro-tolerogenic) macrophages, BIC (microRNA 155 hosting gene) was found up regulated under inflammatory conditions. MicroRNAs are non coding RNAs of ~22nt in length that inhibit gene expression upon pairing to the 3’UTR (UnTranslated Region) of target mRNAs. <i>In silico </i>analysis predicted two pro-Th<sub>2</sub> targets for miR-155: PU.1 and IL13Rα1. PU.1 is a transcription factor essential in myelopoiesis and dendritic cells (DCs) that favours a Th<sub>2</sub> profiling; moreover, PU.1 had been shown to regulate the transcription of DC-SIGN (Dendritic Cell-Specific ICAM-3 Grabbing Non-integrin 1) which is a pathogen receptor expressed in DCs controlled by Th<sub>2</sub> stimuli. IL13Rα1 is the chain receptor for the Th<sub>2</sub> cytokine IL-13, which promotes M2 differentiation. Pro Th<sub>1</sub> stimuli cause maturation of DCs, cells that orchestrate the immune response between Th<sub>1</sub> and Th<sub>2</sub> profiles; moreover, Th<sub>1</sub> stimuli cause classical (M1) macrophages activation versus an alternative (M2) one. My hypothesis was that miR-155 contributes to the pro-Th<sub>1</sub> profile by down regulating pro-Th<sub>2</sub> factors. MiR-155 was found up regulated during DC maturation and both PU.1 and IL13Rα1 were demonstrated as direct targets of miR-155. Employing a developed monocytic cell line which harbors a miR-155 transgene under the control of a Tet-On system (THP1-155 cells), both PU.1 and IL13Rα1 were shown to be down regulated following miR-155 induction in these cells. Moreover, THP1-155 cells showed that DC-SIGN transcription is regulated by miR-155 levels through PU.1 targeting, and that IL-13 signalling cascade through STAT6 transcription factor was down regulated when miR-155 was over expressed. Using Anti miR-155 transfections in DCs, miR-155 was shown to modulate not only DC-SIGN expression, but also DC pathogen binding ability. Using the same technique in macrophages, miR-155 was shown to modulate IL13Rα1 and STAT6 activation, and to regulate the expression of IL-13/STAT6 dependent genes. Therefore, miR-155 contributes to the pro-Th<sub>1</sub> profile by down regulating pro-Th<sub>2</sub> factors, acting as a pro-Th<sub>1</sub>/anti-Th<sub>2</sub> modulator in myeloid cells under inflammatory conditions."],"dc:format":["text"],"dc:identifier.uri":["https://eprints.soton.ac.uk/196569/1/Rocio_Teresa_Martinez-Nunez_PhD_2010.pdf"],"dc:publisher.department":["Clinical & Experimental Sciences (pre 2018 reorg)","School of Medicine"],"dc:publisher.institution":["University of Southampton"],"dc:relation.isreferencedby":["https://eprints.soton.ac.uk/196569/"],"dc:title":["Role of microRNA-155 in dendritic cells and macrophages: MiR-155 directly targets PU.1 and IL13Rα1"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["doctoral"],"dc:type.qualificationname":["Ph.D."]},"updated_at":"2026-07-24T04:36:32Z"}