Absent C3a and C5a receptor signaling into CD4+ T cells enables auto-inductive TGF-β1 signaling and induction of Foxp3+ T regulatory cells

Absent C3a and C5a receptor signaling into CD4+ T cells enables auto-inductive TGF-β1 signaling and induction of Foxp3+ T regulatory cells

C3a and C5a receptor (C3aR and C5aR) signaling by dendritic cells and CD4 + cells provides costimulatory and survival signals to T effector cells. Here, we demonstrate that when C3aR and C5aR signals are not transduced into CD4 + cells, PI-3Kγ-AKT-mTOR signaling ceases, PKA activation increases, aut...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Nature immunology 2012-12, Vol.14 (2), p.162-171
Hauptverfasser: Strainic, Michael G., Shevach, Ethan M., An, Fengqi, Lin, Feng, Medof, M. Edward
Format: Artikel
Sprache:eng
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 171
container_issue 2
container_start_page 162
container_title Nature immunology
container_volume 14
creator Strainic, Michael G.
Shevach, Ethan M.
An, Fengqi
Lin, Feng
Medof, M. Edward
description C3a and C5a receptor (C3aR and C5aR) signaling by dendritic cells and CD4 + cells provides costimulatory and survival signals to T effector cells. Here, we demonstrate that when C3aR and C5aR signals are not transduced into CD4 + cells, PI-3Kγ-AKT-mTOR signaling ceases, PKA activation increases, auto-inductive transforming growth factor- β1 (TGF-β1) signaling initiates, and CD4 + cells become Foxp3 + T regulatory cells (iT regs ). Endogenous TGF-β1 suppresses C3aR and C5aR signaling by preventing C3a and C5a production and upregulating C5L2, an alternate C5a receptor. Absent C3aR and C5aR signaling decreases costimulatory molecule and interleukin-6 production and augments interleukin-10 production. The resulting iT regs exert robust suppression, possess enhanced stability, and suppress ongoing autoimmune disease. Human iT regs with potent suppressor activity can be induced exploiting this insight.
doi_str_mv 10.1038/ni.2499
format Article
fullrecord <record><control><sourceid>pubmedcentral</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4144047</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>pubmedcentral_primary_oai_pubmedcentral_nih_gov_4144047</sourcerecordid><originalsourceid>FETCH-pubmedcentral_primary_oai_pubmedcentral_nih_gov_41440473</originalsourceid><addsrcrecordid>eNqljktOwzAYhC0Eog8QV_j3KMWvpM0GCYUGDpB99Cdxg5FrR7ZT0TNwGw7CmWhFhWDNakYazTdDyA2jC0bF6s7qBZd5fkamLOV5wnOWnf94upqQWQivlDK5zOQlmXDBM5Gm6ZS8PzRB2QiFQEDbQZEieNWqIToPQfcWjbY9aBsdFI_yFipolTEBlMXGqAA4Rpdo241t1DsF1VOZfH6wX9Uj9ZQ7C24DpXsbxBHkVT8aPAztv5lX5GKDJqjrk87JfbmuiudkGJut6trDT4-mHrzeot_XDnX9N7H6pe7drpZMSiqX4t-AL9qUcHc</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Absent C3a and C5a receptor signaling into CD4+ T cells enables auto-inductive TGF-β1 signaling and induction of Foxp3+ T regulatory cells</title><source>Springer Nature - Complete Springer Journals</source><source>Nature Journals Online</source><creator>Strainic, Michael G. ; Shevach, Ethan M. ; An, Fengqi ; Lin, Feng ; Medof, M. Edward</creator><creatorcontrib>Strainic, Michael G. ; Shevach, Ethan M. ; An, Fengqi ; Lin, Feng ; Medof, M. Edward</creatorcontrib><description>C3a and C5a receptor (C3aR and C5aR) signaling by dendritic cells and CD4 + cells provides costimulatory and survival signals to T effector cells. Here, we demonstrate that when C3aR and C5aR signals are not transduced into CD4 + cells, PI-3Kγ-AKT-mTOR signaling ceases, PKA activation increases, auto-inductive transforming growth factor- β1 (TGF-β1) signaling initiates, and CD4 + cells become Foxp3 + T regulatory cells (iT regs ). Endogenous TGF-β1 suppresses C3aR and C5aR signaling by preventing C3a and C5a production and upregulating C5L2, an alternate C5a receptor. Absent C3aR and C5aR signaling decreases costimulatory molecule and interleukin-6 production and augments interleukin-10 production. The resulting iT regs exert robust suppression, possess enhanced stability, and suppress ongoing autoimmune disease. Human iT regs with potent suppressor activity can be induced exploiting this insight.</description><identifier>ISSN: 1529-2908</identifier><identifier>EISSN: 1529-2916</identifier><identifier>DOI: 10.1038/ni.2499</identifier><identifier>PMID: 23263555</identifier><language>eng</language><ispartof>Nature immunology, 2012-12, Vol.14 (2), p.162-171</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27915,27916</link.rule.ids></links><search><creatorcontrib>Strainic, Michael G.</creatorcontrib><creatorcontrib>Shevach, Ethan M.</creatorcontrib><creatorcontrib>An, Fengqi</creatorcontrib><creatorcontrib>Lin, Feng</creatorcontrib><creatorcontrib>Medof, M. Edward</creatorcontrib><title>Absent C3a and C5a receptor signaling into CD4+ T cells enables auto-inductive TGF-β1 signaling and induction of Foxp3+ T regulatory cells</title><title>Nature immunology</title><description>C3a and C5a receptor (C3aR and C5aR) signaling by dendritic cells and CD4 + cells provides costimulatory and survival signals to T effector cells. Here, we demonstrate that when C3aR and C5aR signals are not transduced into CD4 + cells, PI-3Kγ-AKT-mTOR signaling ceases, PKA activation increases, auto-inductive transforming growth factor- β1 (TGF-β1) signaling initiates, and CD4 + cells become Foxp3 + T regulatory cells (iT regs ). Endogenous TGF-β1 suppresses C3aR and C5aR signaling by preventing C3a and C5a production and upregulating C5L2, an alternate C5a receptor. Absent C3aR and C5aR signaling decreases costimulatory molecule and interleukin-6 production and augments interleukin-10 production. The resulting iT regs exert robust suppression, possess enhanced stability, and suppress ongoing autoimmune disease. Human iT regs with potent suppressor activity can be induced exploiting this insight.</description><issn>1529-2908</issn><issn>1529-2916</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNqljktOwzAYhC0Eog8QV_j3KMWvpM0GCYUGDpB99Cdxg5FrR7ZT0TNwGw7CmWhFhWDNakYazTdDyA2jC0bF6s7qBZd5fkamLOV5wnOWnf94upqQWQivlDK5zOQlmXDBM5Gm6ZS8PzRB2QiFQEDbQZEieNWqIToPQfcWjbY9aBsdFI_yFipolTEBlMXGqAA4Rpdo241t1DsF1VOZfH6wX9Uj9ZQ7C24DpXsbxBHkVT8aPAztv5lX5GKDJqjrk87JfbmuiudkGJut6trDT4-mHrzeot_XDnX9N7H6pe7drpZMSiqX4t-AL9qUcHc</recordid><startdate>20121223</startdate><enddate>20121223</enddate><creator>Strainic, Michael G.</creator><creator>Shevach, Ethan M.</creator><creator>An, Fengqi</creator><creator>Lin, Feng</creator><creator>Medof, M. Edward</creator><scope>5PM</scope></search><sort><creationdate>20121223</creationdate><title>Absent C3a and C5a receptor signaling into CD4+ T cells enables auto-inductive TGF-β1 signaling and induction of Foxp3+ T regulatory cells</title><author>Strainic, Michael G. ; Shevach, Ethan M. ; An, Fengqi ; Lin, Feng ; Medof, M. Edward</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmedcentral_primary_oai_pubmedcentral_nih_gov_41440473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Strainic, Michael G.</creatorcontrib><creatorcontrib>Shevach, Ethan M.</creatorcontrib><creatorcontrib>An, Fengqi</creatorcontrib><creatorcontrib>Lin, Feng</creatorcontrib><creatorcontrib>Medof, M. Edward</creatorcontrib><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Strainic, Michael G.</au><au>Shevach, Ethan M.</au><au>An, Fengqi</au><au>Lin, Feng</au><au>Medof, M. Edward</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Absent C3a and C5a receptor signaling into CD4+ T cells enables auto-inductive TGF-β1 signaling and induction of Foxp3+ T regulatory cells</atitle><jtitle>Nature immunology</jtitle><date>2012-12-23</date><risdate>2012</risdate><volume>14</volume><issue>2</issue><spage>162</spage><epage>171</epage><pages>162-171</pages><issn>1529-2908</issn><eissn>1529-2916</eissn><abstract>C3a and C5a receptor (C3aR and C5aR) signaling by dendritic cells and CD4 + cells provides costimulatory and survival signals to T effector cells. Here, we demonstrate that when C3aR and C5aR signals are not transduced into CD4 + cells, PI-3Kγ-AKT-mTOR signaling ceases, PKA activation increases, auto-inductive transforming growth factor- β1 (TGF-β1) signaling initiates, and CD4 + cells become Foxp3 + T regulatory cells (iT regs ). Endogenous TGF-β1 suppresses C3aR and C5aR signaling by preventing C3a and C5a production and upregulating C5L2, an alternate C5a receptor. Absent C3aR and C5aR signaling decreases costimulatory molecule and interleukin-6 production and augments interleukin-10 production. The resulting iT regs exert robust suppression, possess enhanced stability, and suppress ongoing autoimmune disease. Human iT regs with potent suppressor activity can be induced exploiting this insight.</abstract><pmid>23263555</pmid><doi>10.1038/ni.2499</doi><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1529-2908
ispartof Nature immunology, 2012-12, Vol.14 (2), p.162-171
issn 1529-2908
1529-2916
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4144047
source Springer Nature - Complete Springer Journals; Nature Journals Online
title Absent C3a and C5a receptor signaling into CD4+ T cells enables auto-inductive TGF-β1 signaling and induction of Foxp3+ T regulatory cells
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T07%3A39%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmedcentral&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Absent%20C3a%20and%20C5a%20receptor%20signaling%20into%20CD4+%20T%20cells%20enables%20auto-inductive%20TGF-%CE%B21%20signaling%20and%20induction%20of%20Foxp3+%20T%20regulatory%20cells&rft.jtitle=Nature%20immunology&rft.au=Strainic,%20Michael%20G.&rft.date=2012-12-23&rft.volume=14&rft.issue=2&rft.spage=162&rft.epage=171&rft.pages=162-171&rft.issn=1529-2908&rft.eissn=1529-2916&rft_id=info:doi/10.1038/ni.2499&rft_dat=%3Cpubmedcentral%3Epubmedcentral_primary_oai_pubmedcentral_nih_gov_4144047%3C/pubmedcentral%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/23263555&rfr_iscdi=true