Loss of direct adrenergic innervation after peripheral nerve injury causes lymph node expansion through IFN-γ
Peripheral nerve injury can cause debilitating disease and immune cell-mediated destruction of the affected nerve. While the focus has been on the nerve-regenerative response, the effect of loss of innervation on lymph node function is unclear. Here, we show that the popliteal lymph node (popLN) rec...
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| Veröffentlicht in: | The Journal of experimental medicine 2021-08, Vol.218 (8) |
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| creator | Chen, Chien-Sin Weber, Jasmin Holtkamp, Stephan Jonas Ince, Louise Madeleine de Juan, Alba Wang, Chen Lutes, Lydia Barnoud, Coline Kizil, Burak Hergenhan, Sophia Martina Salvermoser, Johanna Lasch, Manuel Deindl, Elisabeth Schraml, Barbara Baumjohann, Dirk Scheiermann, Christoph |
| description | Peripheral nerve injury can cause debilitating disease and immune cell-mediated destruction of the affected nerve. While the focus has been on the nerve-regenerative response, the effect of loss of innervation on lymph node function is unclear. Here, we show that the popliteal lymph node (popLN) receives direct neural input from the sciatic nerve and that sciatic denervation causes lymph node expansion. Loss of sympathetic, adrenergic tone induces the expression of IFN-γ in LN CD8 T cells, which is responsible for LN expansion. Surgery-induced IFN-γ expression and expansion can be rescued by β2 adrenergic receptor agonists but not sensory nerve agonists. These data demonstrate the mechanisms governing the pro-inflammatory effect of loss of direct adrenergic input on lymph node function. |
| doi_str_mv | 10.1084/jem.20202377 |
| format | Article |
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While the focus has been on the nerve-regenerative response, the effect of loss of innervation on lymph node function is unclear. Here, we show that the popliteal lymph node (popLN) receives direct neural input from the sciatic nerve and that sciatic denervation causes lymph node expansion. Loss of sympathetic, adrenergic tone induces the expression of IFN-γ in LN CD8 T cells, which is responsible for LN expansion. Surgery-induced IFN-γ expression and expansion can be rescued by β2 adrenergic receptor agonists but not sensory nerve agonists. These data demonstrate the mechanisms governing the pro-inflammatory effect of loss of direct adrenergic input on lymph node function.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.20202377</identifier><identifier>PMID: 34086056</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Adrenergic Agents - metabolism ; Animals ; Antigens - immunology ; Autoimmunity ; Axotomy ; CD8-Positive T-Lymphocytes - immunology ; Denervation ; Inflammation - pathology ; Interferon-gamma - metabolism ; Lymph Nodes - pathology ; Male ; Mice ; Mice, Inbred C57BL ; Neuroinflammation ; Peripheral Nerve Injuries - pathology ; Sciatic Nerve - immunology ; Sciatic Nerve - pathology ; Signal Transduction</subject><ispartof>The Journal of experimental medicine, 2021-08, Vol.218 (8)</ispartof><rights>2021 Chen et al.</rights><rights>2021 Chen et al. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-b0b6de3f1aa58987e14dfd0b44b551e836a2ecbb19c9c41ff63f626fc0ec0ac03</citedby><cites>FETCH-LOGICAL-c384t-b0b6de3f1aa58987e14dfd0b44b551e836a2ecbb19c9c41ff63f626fc0ec0ac03</cites><orcidid>0000-0001-5500-0217 ; 0000-0003-3100-1375 ; 0000-0002-2093-0876 ; 0000-0001-8385-8288 ; 0000-0003-4378-6106 ; 0000-0002-5847-1441 ; 0000-0002-1856-1493 ; 0000-0003-0174-4389 ; 0000-0002-0626-2162 ; 0000-0002-2134-0966 ; 0000-0001-6133-6294 ; 0000-0003-2348-1305 ; 0000-0003-1699-548X ; 0000-0003-2271-5587 ; 0000-0002-5801-0151 ; 0000-0002-9212-0995</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34086056$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Chien-Sin</creatorcontrib><creatorcontrib>Weber, Jasmin</creatorcontrib><creatorcontrib>Holtkamp, Stephan Jonas</creatorcontrib><creatorcontrib>Ince, Louise Madeleine</creatorcontrib><creatorcontrib>de Juan, Alba</creatorcontrib><creatorcontrib>Wang, Chen</creatorcontrib><creatorcontrib>Lutes, Lydia</creatorcontrib><creatorcontrib>Barnoud, Coline</creatorcontrib><creatorcontrib>Kizil, Burak</creatorcontrib><creatorcontrib>Hergenhan, Sophia Martina</creatorcontrib><creatorcontrib>Salvermoser, Johanna</creatorcontrib><creatorcontrib>Lasch, Manuel</creatorcontrib><creatorcontrib>Deindl, Elisabeth</creatorcontrib><creatorcontrib>Schraml, Barbara</creatorcontrib><creatorcontrib>Baumjohann, Dirk</creatorcontrib><creatorcontrib>Scheiermann, Christoph</creatorcontrib><title>Loss of direct adrenergic innervation after peripheral nerve injury causes lymph node expansion through IFN-γ</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>Peripheral nerve injury can cause debilitating disease and immune cell-mediated destruction of the affected nerve. While the focus has been on the nerve-regenerative response, the effect of loss of innervation on lymph node function is unclear. Here, we show that the popliteal lymph node (popLN) receives direct neural input from the sciatic nerve and that sciatic denervation causes lymph node expansion. Loss of sympathetic, adrenergic tone induces the expression of IFN-γ in LN CD8 T cells, which is responsible for LN expansion. Surgery-induced IFN-γ expression and expansion can be rescued by β2 adrenergic receptor agonists but not sensory nerve agonists. These data demonstrate the mechanisms governing the pro-inflammatory effect of loss of direct adrenergic input on lymph node function.</description><subject>Adrenergic Agents - metabolism</subject><subject>Animals</subject><subject>Antigens - immunology</subject><subject>Autoimmunity</subject><subject>Axotomy</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Denervation</subject><subject>Inflammation - pathology</subject><subject>Interferon-gamma - metabolism</subject><subject>Lymph Nodes - pathology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Neuroinflammation</subject><subject>Peripheral Nerve Injuries - pathology</subject><subject>Sciatic Nerve - immunology</subject><subject>Sciatic Nerve - pathology</subject><subject>Signal Transduction</subject><issn>0022-1007</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU1v1DAQhi0Eokvhxhn5yKEpdvwR54KEKloqreDSni3HGW-8SuxgJxX7u_gf_U31qh8CzWFGmmfeGc2L0EdKzilR_MsepvOalGBN8wptqOCkagVTr9GGkLquKCHNCXqX854QyrmQb9EJ40RJIuQGhW3MGUeHe5_ALtj0CQKknbfYh1LcmcXHgI1bIOEZkp8HSGbExxYUZL-mA7ZmzZDxeJjmAYfYA4Y_swn5OLkMKa67AV9f_qzu_75Hb5wZM3x4yqfo9vL7zcWPavvr6vri27ayTPGl6kgne2COGiNUqxqgvHc96TjvhKCgmDQ12K6jrW0tp85J5mQtnSVgibGEnaKvj7rz2k3QWwhLuVrPyU8mHXQ0Xv_fCX7Qu3inFVWiVaoIfH4SSPH3CnnRk88WxtEEiGvWtWCNZFIxWtCzR9Sm8ssE7mUNJfpokS4W6WeLCv7p39Ne4GdP2AMuLpFO</recordid><startdate>20210802</startdate><enddate>20210802</enddate><creator>Chen, Chien-Sin</creator><creator>Weber, Jasmin</creator><creator>Holtkamp, Stephan Jonas</creator><creator>Ince, Louise Madeleine</creator><creator>de Juan, Alba</creator><creator>Wang, Chen</creator><creator>Lutes, Lydia</creator><creator>Barnoud, Coline</creator><creator>Kizil, Burak</creator><creator>Hergenhan, Sophia Martina</creator><creator>Salvermoser, Johanna</creator><creator>Lasch, Manuel</creator><creator>Deindl, Elisabeth</creator><creator>Schraml, Barbara</creator><creator>Baumjohann, Dirk</creator><creator>Scheiermann, Christoph</creator><general>Rockefeller University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-5500-0217</orcidid><orcidid>https://orcid.org/0000-0003-3100-1375</orcidid><orcidid>https://orcid.org/0000-0002-2093-0876</orcidid><orcidid>https://orcid.org/0000-0001-8385-8288</orcidid><orcidid>https://orcid.org/0000-0003-4378-6106</orcidid><orcidid>https://orcid.org/0000-0002-5847-1441</orcidid><orcidid>https://orcid.org/0000-0002-1856-1493</orcidid><orcidid>https://orcid.org/0000-0003-0174-4389</orcidid><orcidid>https://orcid.org/0000-0002-0626-2162</orcidid><orcidid>https://orcid.org/0000-0002-2134-0966</orcidid><orcidid>https://orcid.org/0000-0001-6133-6294</orcidid><orcidid>https://orcid.org/0000-0003-2348-1305</orcidid><orcidid>https://orcid.org/0000-0003-1699-548X</orcidid><orcidid>https://orcid.org/0000-0003-2271-5587</orcidid><orcidid>https://orcid.org/0000-0002-5801-0151</orcidid><orcidid>https://orcid.org/0000-0002-9212-0995</orcidid></search><sort><creationdate>20210802</creationdate><title>Loss of direct adrenergic innervation after peripheral nerve injury causes lymph node expansion through IFN-γ</title><author>Chen, Chien-Sin ; 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While the focus has been on the nerve-regenerative response, the effect of loss of innervation on lymph node function is unclear. Here, we show that the popliteal lymph node (popLN) receives direct neural input from the sciatic nerve and that sciatic denervation causes lymph node expansion. Loss of sympathetic, adrenergic tone induces the expression of IFN-γ in LN CD8 T cells, which is responsible for LN expansion. Surgery-induced IFN-γ expression and expansion can be rescued by β2 adrenergic receptor agonists but not sensory nerve agonists. 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| subjects | Adrenergic Agents - metabolism Animals Antigens - immunology Autoimmunity Axotomy CD8-Positive T-Lymphocytes - immunology Denervation Inflammation - pathology Interferon-gamma - metabolism Lymph Nodes - pathology Male Mice Mice, Inbred C57BL Neuroinflammation Peripheral Nerve Injuries - pathology Sciatic Nerve - immunology Sciatic Nerve - pathology Signal Transduction |
| title | Loss of direct adrenergic innervation after peripheral nerve injury causes lymph node expansion through IFN-γ |
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