{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:01:20Z","timestamp":1788865280546,"version":"build-2803163510"},"reference-count":62,"publisher":"American Society for Clinical Investigation","issue":"1","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,11]]},"abstract":"<jats:p>\n                    The CNS is regarded as an immunoprivileged organ, evading routine immune surveillance; however, the coordinated development of immune responses profoundly influences outcomes after brain injury. Innate lymphoid cells (ILCs) are cytokine-producing cells that are critical for the initiation, modulation, and resolution of inflammation, but the functional relevance and mechanistic regulation of ILCs are unexplored after acute brain injury. We demonstrate increased proliferation of all ILC subtypes within the meninges for up to 1 year after experimental traumatic brain injury (TBI) while ILCs were present within resected dura and elevated within cerebrospinal fluid (CSF) of moderate-to-severe TBI patients. In line with energetic derangements after TBI, inhibition of the metabolic regulator, AMPK, increased meningeal ILC expansion, whereas AMPK activation suppressed proinflammatory ILC1\/ILC3 and increased the frequency of IL-10\u2013expressing ILC2 after TBI. Moreover, intracisternal administration of IL-33 activated AMPK, expanded ILC2, and suppressed ILC1 and ILC3 within the meninges of WT and Rag1\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice, but not Rag1\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    IL2rg\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice. Taken together, we identify AMPK as a brake on the expansion of proinflammatory, CNS-resident ILCs after brain injury. These findings establish a mechanistic framework whereby immunometabolic modulation of ILCs may direct the specificity, timing, and magnitude of cerebral immunity.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.126766","type":"journal-article","created":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T14:01:27Z","timestamp":1610287287000},"source":"Crossref","is-referenced-by-count":52,"title":["AMPK induces regulatory innate lymphoid cells after traumatic brain injury"],"prefix":"10.1172","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3144-2288","authenticated-orcid":true,"given":"Babak","family":"Baban","sequence":"first","affiliation":[{"name":"Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia, Augusta University, Augusta, Georgia, USA."},{"name":"Department of Surgery,"},{"name":"Department of Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly","family":"Braun","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hesam","family":"Khodadadi","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia, Augusta University, Augusta, Georgia, USA."},{"name":"Department of Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayobami","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katelyn","family":"Alverson","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneeq","family":"Malik","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia, Augusta University, Augusta, Georgia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khoi","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Skon","family":"Nazarian","sequence":"additional","affiliation":[{"name":"Department of Radiology and Imaging, Medical College of Georgia, Augusta University, Augusta, Georgia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Hess","sequence":"additional","affiliation":[{"name":"Department of Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0054-4692","authenticated-orcid":true,"given":"Scott","family":"Forseen","sequence":"additional","affiliation":[{"name":"Department of Radiology and Imaging, Medical College of Georgia, Augusta University, Augusta, Georgia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander F.","family":"Post","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando L.","family":"Vale","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Vender","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Nasrul","family":"Hoda","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4359-9725","authenticated-orcid":true,"given":"Omid","family":"Akbari","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4206-3830","authenticated-orcid":true,"given":"Kumar","family":"Vaibhav","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia, Augusta University, Augusta, Georgia, USA."},{"name":"Department of Neurosurgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishnan M.","family":"Dhandapani","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.ss6609a1"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf6260"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.07.010"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nature13047"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa6566"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2015.01.004"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.030"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nature14115"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nature08636"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nature08949"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nature11813"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.09.005"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3892"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nature14432"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20142290"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600073"},{"issue":"Pt 2","key":"B17","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1093\/brain\/awq353","article-title":"Cerebral extracellular chemistry and outcome following traumatic brain injury: a microdialysis study of 223 patients","volume":"134","author":"Timofeev","year":"2011","journal-title":"Brain"},{"key":"B18","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2015.00094","article-title":"Brain metabolic stress and neuroinflammation at the basis of cognitive impairment in Alzheimer\u2019s disease","volume":"7","author":"De Felice","year":"2015","journal-title":"Front Aging Neurosci"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2019.1582332"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1986.64.5.0787"},{"key":"B21","doi-asserted-by":"crossref","DOI":"10.1186\/1742-2094-10-32","article-title":"In vivo temporal and spatial profile of leukocyte adhesion and migration after experimental traumatic brain injury in mice","volume":"10","author":"Schwarzmaier","year":"2013","journal-title":"J Neuroinflammation"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/nature11862"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501549"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20171905"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(06)61009-1"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000616"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.2668"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.1948"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2017.11.003"},{"issue":"Pt 1","key":"B30","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1093\/brain\/aws322","article-title":"Inflammation and white matter degeneration persist for years after a single traumatic brain injury","volume":"136","author":"Johnson","year":"2013","journal-title":"Brain"},{"key":"B31","doi-asserted-by":"crossref","DOI":"10.1186\/s12974-015-0445-y","article-title":"Thalamic inflammation after brain trauma is associated with thalamo-cortical white matter damage","volume":"12","author":"Scott","year":"2015","journal-title":"J Neuroinflammation"},{"key":"B32","article-title":"Do corticosteroids play a role in the management of traumatic brain injury?","volume":"7","author":"Hoshide","year":"2016","journal-title":"Surg Neurol Int"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22581"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3171\/2009.10.FOCUS09223"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1177\/1753425916669862"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1097\/01.shk.0000161385.62758.24"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601948"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-017-8468-4"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3816"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3078"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1172\/JCI89717"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00678-2"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101270"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.01.013"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3094"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2016.49.5.023"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02023-z"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.07.027"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/S1734-1140(10)70357-1"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803563"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2006.10.039"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0282-9"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/nri3365"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2534"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.06.019"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3444"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13726"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40671"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa070716"},{"key":"B60","doi-asserted-by":"crossref","unstructured":"Derecki N, Kipnis J. Mouse meninges isolation for FACS [published September 08, 2014]. Protocol Exchange. https:\/\/doi.org\/10.1038\/protex.2014.030","DOI":"10.1038\/protex.2014.030"},{"key":"B61","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2180-4-36","article-title":"Method for inducing experimental pneumococcal meningitis in outbred mice","volume":"4","author":"Chiavolini","year":"2004","journal-title":"BMC Microbiol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2017.10.021"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/126766\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:48:57Z","timestamp":1779151737000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/126766"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,11]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1,11]]},"published-print":{"date-parts":[[2021,1,11]]}},"alternative-id":["10.1172\/jci.insight.126766"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.126766","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,11]]},"article-number":"e126766"}}