{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:17:44Z","timestamp":1787584664059,"version":"build-2736575974"},"reference-count":102,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T00:00:00Z","timestamp":1581379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fibromyalgia is one of the most important \u201crheumatic\u201d disorders, after osteoarthritis. The etiology of the disease is still not clear. At the moment, the most defined pathological mechanism is the alteration of central pain pathways, and emotional conditions can trigger or worsen symptoms. Increasing evidence supports the role of mast cells in maintaining pain conditions such as musculoskeletal pain and central sensitization. Importantly, mast cells can mediate microglia activation through the production of proinflammatory cytokines such as IL-1\u03b2, IL-6, and TNF\u03b1. In addition, levels of chemokines and proinflammatory cytokines are enhanced in serum and could contribute to inflammation at systemic level. Despite the well-characterized relationship between the nervous system and inflammation, the mechanism that links the different pathological features of fibromyalgia, including stress-related manifestations, central sensitization, and dysregulation of the innate and adaptive immune responses is largely unknown. This review aims to provide an overview of the current understanding of the role of adaptive immune cells, in particular T cells, in the physiopathology of fibromyalgia. It also aims at linking the latest advances emerging from basic science to envisage new perspectives to explain the role of T cells in interconnecting the psychological, neurological, and inflammatory symptoms of fibromyalgia.<\/jats:p>","DOI":"10.3390\/ijms21041186","type":"journal-article","created":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T09:25:21Z","timestamp":1581413121000},"page":"1186","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["T Cell Subpopulations in the Physiopathology of Fibromyalgia: Evidence and Perspectives"],"prefix":"10.3390","volume":"21","author":[{"given":"Giuseppe","family":"Banfi","sequence":"first","affiliation":[{"name":"IRCCS Istituto Ortopedico Galeazzi, 20161Milan, Italy"},{"name":"School of Medicine, Universit\u00e0 Vita-Salute San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Diani","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Ortopedico Galeazzi, 20161Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo D.","family":"Pigatto","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Ortopedico Galeazzi, 20161Milan, Italy"},{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Reali","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Ortopedico Galeazzi, 20161Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1001\/jama.2014.3266","article-title":"Fibromyalgia: A clinical review","volume":"311","author":"Clauw","year":"2014","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1097\/j.pain.0000000000000992","article-title":"Visceral pain as a triggering factor for fibromyalgia symptoms in comorbid patients","volume":"158","author":"Costantini","year":"2017","journal-title":"Pain"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1159\/000115041","article-title":"Lymphocyte subsets and the role of TH1\/TH2 balance in stressed chronic pain patients","volume":"14","author":"Kaufmann","year":"2007","journal-title":"Neuroimmunomodulation"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Bote, M.E., Garcia, J.J., Hinchado, M.D., and Ortega, E. (2013). Fibromyalgia: Anti-inflammatory and stress responses after acute moderate exercise. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0074524"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1159\/000341664","article-title":"Inflammatory\/stress feedback dysregulation in women with fibromyalgia","volume":"19","author":"Bote","year":"2012","journal-title":"Neuroimmunomodulation"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"353","DOI":"10.3389\/fncel.2019.00353","article-title":"Mast Cells, Neuroinflammation and Pain in Fibromyalgia Syndrome","volume":"13","author":"Theoharides","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1124\/jpet.115.227298","article-title":"Fibromyalgia syndrome in need of effective treatments","volume":"355","author":"Theoharides","year":"2015","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1111\/j.1365-2249.2008.03787.x","article-title":"May genetic factors in fibromyalgia help to identify patients with differentially altered frequencies of immune cells?","volume":"154","author":"Carvalho","year":"2008","journal-title":"Clin. Exp. Immunol."},{"key":"ref_9","first-page":"S9","article-title":"CD3+CD56+natural killer T cells in fibromyalgia syndrome patients: Association with the intensity of depression","volume":"31","author":"Nugraha","year":"2013","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Uceyler, N., Hauser, W., and Sommer, C. (2011). Systematic review with meta-analysis: Cytokines in fibromyalgia syndrome. BMC Musculoskelet. Disord., 12.","DOI":"10.1186\/1471-2474-12-245"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/nature18626","article-title":"Unexpected role of interferon-gamma in regulating neuronal connectivity and social behaviour","volume":"535","author":"Filiano","year":"2016","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1126\/science.aag2638","article-title":"Multifaceted interactions between adaptive immunity and the central nervous system","volume":"353","author":"Kipnis","year":"2016","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Totsch, S.K., and Sorge, R.E. (2017). Immune System Involvement in Specific Pain Conditions. Mol. Pain, 13.","DOI":"10.1177\/1744806917724559"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3389\/fncel.2018.00035","article-title":"Potential Mechanisms Underlying Centralized Pain and Emerging Therapeutic Interventions","volume":"12","author":"Nicol","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_15","first-page":"225","article-title":"Cytokine patterns in fibromyalgia and their correlation with clinical manifestations","volume":"25","author":"Bazzichi","year":"2007","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1124\/jpet.115.230060","article-title":"Neuropeptides CRH, SP, HK-1, and Inflammatory Cytokines IL-6 and TNF Are Increased in Serum of Patients with Fibromyalgia Syndrome, Implicating Mast Cells","volume":"356","author":"Tsilioni","year":"2016","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2776","DOI":"10.1038\/sj.npp.1301200","article-title":"Cerebrospinal fluid corticotropin-releasing factor concentration is associated with pain but not fatigue symptoms in patients with fibromyalgia","volume":"31","author":"McLean","year":"2006","journal-title":"Neuropsychopharmacology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/1744-8069-4-52","article-title":"Prolonged gabapentin analgesia in an experimental mouse model of fibromyalgia","volume":"4","author":"Nishiyori","year":"2008","journal-title":"Mol. Pain"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.bbr.2009.07.005","article-title":"Chronic restraint stress induces mechanical and cold allodynia, and enhances inflammatory pain in rat: Relevance to human stress-associated painful pathologies","volume":"205","author":"Bardin","year":"2009","journal-title":"Behav. Brain Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.neuroscience.2011.04.020","article-title":"Stress enhances muscle nociceptor activity in the rat","volume":"185","author":"Chen","year":"2011","journal-title":"Neuroscience"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Andres-Rodriguez, L., and Borras, X. (2019). Machine Learning to Understand the Immune-Inflammatory Pathways in Fibromyalgia. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20174231"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"9","DOI":"10.2174\/1874226201003010009","article-title":"Preliminary Evidence of Increased Pain and Elevated Cytokines in Fibromyalgia Patients with Defective Growth Hormone Response to Exercise","volume":"3","author":"Ross","year":"2010","journal-title":"Open Immunol. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.jneuroim.2011.10.013","article-title":"Evidence of central inflammation in fibromyalgia-increased cerebrospinal fluid interleukin-8 levels","volume":"242","author":"Kadetoff","year":"2012","journal-title":"J. Neuroimmunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.imlet.2014.01.009","article-title":"Fibromyalgia and cytokines","volume":"161","author":"Howard","year":"2014","journal-title":"Immunol. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.it.2005.08.001","article-title":"Chemokines, chemokine receptors and pain","volume":"26","author":"Abbadie","year":"2005","journal-title":"Trends Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1056\/NEJMra052723","article-title":"The many roles of chemokines and chemokine receptors in inflammation","volume":"354","author":"Charo","year":"2006","journal-title":"N Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1097\/BSD.0b013e3181e15cc8","article-title":"Serum monocyte chemotactic protein-1 concentrations distinguish patients with ankylosing spondylitis from patients with mechanical low back pain","volume":"24","author":"Tsou","year":"2011","journal-title":"J. Spinal Disord. Tech."},{"key":"ref_28","first-page":"S60","article-title":"Increased levels of IL-17A in patients with fibromyalgia","volume":"31","author":"Pernambuco","year":"2013","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/j.1756-185X.2011.01673.x","article-title":"The role of interleukin (IL)-17 in anxiety and depression of patients with rheumatoid arthritis","volume":"15","author":"Liu","year":"2012","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.pain.2012.10.022","article-title":"Spinal interleukin-17 promotes thermal hyperalgesia and NMDA NR1 phosphorylation in an inflammatory pain rat model","volume":"154","author":"Meng","year":"2013","journal-title":"Pain"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.nicl.2015.02.022","article-title":"Fibromyalgia is characterized by altered frontal and cerebellar structural covariance brain networks","volume":"7","author":"Kim","year":"2015","journal-title":"Neuroimage Clin."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1002\/ejp.1086","article-title":"Evidence for the modulation of nociception in mice by central mast cells","volume":"21","author":"Kissel","year":"2017","journal-title":"Eur. J. Pain"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/bs.pmbts.2014.11.007","article-title":"Nonneuronal central mechanisms of pain: Glia and immune response","volume":"131","author":"Sweitzer","year":"2015","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jneuroim.2013.09.018","article-title":"A focus on mast cells and pain","volume":"264","author":"Heron","year":"2013","journal-title":"J. Neuroimmunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.molimm.2014.03.001","article-title":"Mast cells: Versatile gatekeepers of pain","volume":"63","author":"Chatterjea","year":"2015","journal-title":"Mol. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"389","DOI":"10.2340\/00015555-0653","article-title":"Chronic urticaria is usually associated with fibromyalgia syndrome","volume":"89","author":"Torresani","year":"2009","journal-title":"Acta Derm. Venereol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1007\/s10067-010-1474-7","article-title":"Abnormal overexpression of mastocytes in skin biopsies of fibromyalgia patients","volume":"29","author":"Blanco","year":"2010","journal-title":"Clin. Rheumatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.3181\/0712-RM-328","article-title":"High plasma levels of MCP-1 and eotaxin provide evidence for an immunological basis of fibromyalgia","volume":"233","author":"Zhang","year":"2008","journal-title":"Exp. Biol. Med. (Maywood)"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.pain.2014.03.004","article-title":"Role for monocyte chemoattractant protein-1 in the induction of chronic muscle pain in the rat","volume":"155","author":"Alvarez","year":"2014","journal-title":"Pain"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.ejphar.2011.10.001","article-title":"Involvement of mast cells in a mouse model of postoperative pain","volume":"672","author":"Oliveira","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1126\/science.1227901","article-title":"Microglia: Scapegoat, saboteur, or something else?","volume":"339","author":"Aguzzi","year":"2013","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.bbalip.2014.07.008","article-title":"Prostaglandin E2-induced inflammation: Relevance of prostaglandin E receptors","volume":"1851","author":"Kawahara","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ryabkova, V.A., Churilov, L.P., and Shoenfeld, Y. (2019). Neuroimmunology: What Role for Autoimmunity, Neuroinflammation, and Small Fiber Neuropathy in Fibromyalgia, Chronic Fatigue Syndrome, and Adverse Events after Human Papillomavirus Vaccination?. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20205164"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"515","DOI":"10.2147\/JPR.S128508","article-title":"Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma","volume":"10","author":"Backryd","year":"2017","journal-title":"J. Pain Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1007\/s12035-016-9720-x","article-title":"Suppression of Brain Mast Cells Degranulation Inhibits Microglial Activation and Central Nervous System Inflammation","volume":"54","author":"Dong","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1159\/000443093","article-title":"Induction of Microglial Activation by Mediators Released from Mast Cells","volume":"38","author":"Zhang","year":"2016","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.celrep.2017.07.004","article-title":"The Lifespan and Turnover of Microglia in the Human Brain","volume":"20","author":"Reu","year":"2017","journal-title":"Cell Rep."},{"key":"ref_48","first-page":"1407","article-title":"Neuroinflammation as modifier of genetically caused neurological disorders of the central nervous system: Understanding pathogenesis and chances for treatment","volume":"65","author":"Groh","year":"2017","journal-title":"Gila"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1046\/j.0022-3042.2001.00687.x","article-title":"Functional expression of corticotropin-releasing hormone (CRH) receptor 1 in cultured rat microglia","volume":"80","author":"Wang","year":"2002","journal-title":"J. Neurochem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1097\/WCO.0000000000000599","article-title":"Neuroinflammatory mechanisms in amyotrophic lateral sclerosis pathogenesis","volume":"31","author":"Thonhoff","year":"2018","journal-title":"Curr. Opin. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.sjpain.2010.01.002","article-title":"Long-term pain, neuroinflammation and glial activation","volume":"1","author":"Hansson","year":"2010","journal-title":"Scand. J. Pain"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1186\/s12974-018-1378-z","article-title":"Sequential alteration of microglia and astrocytes in the rat thalamus following spinal nerve ligation","volume":"15","author":"Blaszczyk","year":"2018","journal-title":"J. Neuroinflammation"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"72","DOI":"10.3389\/fncel.2018.00072","article-title":"An Inflammation-Centric View of Neurological Disease: Beyond the Neuron","volume":"12","author":"Skaper","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.cell.2019.06.022","article-title":"Cutaneous TRPV1(+) Neurons Trigger Protective Innate Type 17 Anticipatory Immunity","volume":"178","author":"Cohen","year":"2019","journal-title":"Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.autrev.2018.01.009","article-title":"Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome\u2014Evidence for an autoimmune disease","volume":"17","author":"Sotzny","year":"2018","journal-title":"Autoimmun. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4362","DOI":"10.4049\/jimmunol.170.8.4362","article-title":"Human T cells express a functional ionotropic glutamate receptor GluR3, and glutamate by itself triggers integrin-mediated adhesion to laminin and fibronectin and chemotactic migration","volume":"170","author":"Ganor","year":"2003","journal-title":"J. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"12603","DOI":"10.1074\/jbc.M115.636506","article-title":"Macrophage-T cell interactions mediate neuropathic pain through the glucocorticoid-induced tumor necrosis factor ligand system","volume":"290","author":"Kobayashi","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_58","unstructured":"Draleau, K., Maddula, S., Slaiby, A., Nutile-McMenemy, N., De Leo, J., and Cao, L. (2014). Phenotypic Identification of Spinal Cord-Infiltrating CD4(+) T Lymphocytes in a Murine Model of Neuropathic Pain. J. Pain Relief."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1038\/nn.4053","article-title":"Different immune cells mediate mechanical pain hypersensitivity in male and female mice","volume":"18","author":"Sorge","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1002\/art.1780340712","article-title":"Altered interleukin-2 secretion in patients with primary fibromyalgia syndrome","volume":"34","author":"Hader","year":"1991","journal-title":"Arthritis Rheum."},{"key":"ref_61","first-page":"2122","article-title":"Lymphocyte subpopulations in patients with primary fibromyalgia","volume":"21","author":"Hernanz","year":"1994","journal-title":"J. Rheumatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1089\/107999099313523","article-title":"Lymphocyte markers and natural killer cell activity in fibromyalgia syndrome: Effects of low-dose, sublingual use of human interferon-alpha","volume":"19","author":"Russell","year":"1999","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1006\/exmp.2000.2322","article-title":"Environmental immunogens and T-cell-mediated responses in fibromyalgia: Evidence for immune dysregulation and determinants of granuloma formation","volume":"69","author":"Shanklin","year":"2000","journal-title":"Exp. Mol. Pathol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.envres.2017.12.004","article-title":"Delayed-type hypersensitivity to metals in connective tissue diseases and fibromyalgia","volume":"161","author":"Bjorklund","year":"2018","journal-title":"Environ. Res."},{"key":"ref_65","first-page":"753","article-title":"Metals as a common trigger of inflammation resulting in non-specific symptoms: Diagnosis and treatment","volume":"16","author":"Stejskal","year":"2014","journal-title":"Isr. Med. Assoc. J."},{"key":"ref_66","first-page":"559","article-title":"Metal-induced inflammation triggers fibromyalgia in metal-allergic patients","volume":"34","author":"Stejskal","year":"2013","journal-title":"Neuro Endocrinol. Lett."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"356235","DOI":"10.1155\/2013\/356235","article-title":"Allergological and toxicological aspects in a multiple chemical sensitivity cohort","volume":"2013","author":"Pigatto","year":"2013","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1196\/annals.1314.011","article-title":"Posttraumatic stress disorder and physical illness: Results from clinical and epidemiologic studies","volume":"1032","author":"Boscarino","year":"2004","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.3899\/jrheum.120022","article-title":"Rheumatic manifestations of autoimmune thyroid disease: The other autoimmune disease","volume":"39","author":"Tagoe","year":"2012","journal-title":"J. Rheumatol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1177\/0004563213506413","article-title":"Altered profile of chemokines in fibromyalgia patients","volume":"51","author":"Garcia","year":"2014","journal-title":"Ann. Clin. Biochem."},{"key":"ref_71","first-page":"939","article-title":"Concentration of cytokines in patients with osteoarthritis of the knee and fibromyalgia","volume":"9","author":"Imamura","year":"2014","journal-title":"Clin. Interv. Aging"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Sugimoto, C., Konno, T., Wakao, R., Fujita, H., Fujita, H., and Wakao, H. (2015). Mucosal-associated invariant T cell is a potential marker to distinguish fibromyalgia syndrome from arthritis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0121124"},{"key":"ref_73","first-page":"81","article-title":"T helper 1 response is correlated with widespread pain, fatigue, sleeping disorders and the quality of life in patients with fibromyalgia and is modulated by hyperbaric oxygen therapy","volume":"37","author":"Guggino","year":"2019","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.autrev.2016.02.008","article-title":"Cannabinoids and autoimmune diseases: A systematic review","volume":"15","author":"Katchan","year":"2016","journal-title":"Autoimmun. Rev."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1002\/cpt.568","article-title":"Medical cannabis: Another piece in the mosaic of autoimmunity?","volume":"101","author":"Katz","year":"2017","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0165-0327(97)00144-4","article-title":"Immune markers in fibromyalgia: Comparison with major depressed patients and normal volunteers","volume":"48","author":"Bonaccorso","year":"1998","journal-title":"J. Affect. Disord."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.autrev.2008.07.023","article-title":"Etiology of fibromyalgia: The possible role of infection and vaccination","volume":"8","author":"Buskila","year":"2008","journal-title":"Autoimmun. Rev."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"451","DOI":"10.2147\/JPR.S127288","article-title":"A famciclovir + celecoxib combination treatment is safe and efficacious in the treatment of fibromyalgia","volume":"10","author":"Pridgen","year":"2017","journal-title":"J. Pain Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1007\/s10067-019-04447-y","article-title":"Silicone breast implants and depression, fibromyalgia and chronic fatigue syndrome in a rheumatology clinic population","volume":"38","author":"Khoo","year":"2019","journal-title":"Clin. Rheumatol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Wolfe, F., Walitt, B., Perrot, S., Rasker, J.J., and Hauser, W. (2018). Fibromyalgia diagnosis and biased assessment: Sex, prevalence and bias. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0203755"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1300\/J094v04n03_03","article-title":"HLA Studies in Fibromyalgia","volume":"4","author":"Branco","year":"1996","journal-title":"J. Musculoskelet. Pain"},{"key":"ref_82","first-page":"1269","article-title":"HLA antigens in primary fibromyalgia syndrome","volume":"19","author":"Horven","year":"1992","journal-title":"J. Rheumatol."},{"key":"ref_83","first-page":"228","article-title":"Absence of correlation between HLA antigens and fibromyalgia syndrome in Italian patients","volume":"9","author":"Biasi","year":"1994","journal-title":"Ann. Ital. Med. Int."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nri1571","article-title":"Stress-induced immune dysfunction: Implications for health","volume":"5","author":"Glaser","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/S1471-4906(03)00173-X","article-title":"How stress influences the immune response","volume":"24","author":"Padgett","year":"2003","journal-title":"Trends Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.cell.2019.10.001","article-title":"Stress-Induced Metabolic Disorder in Peripheral CD4(+) T Cells Leads to Anxiety-like Behavior","volume":"179","author":"Fan","year":"2019","journal-title":"Cell"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1111\/j.1472-8206.2007.00526.x","article-title":"Animal models of anxiety in mice","volume":"21","author":"Bourin","year":"2007","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"S101","DOI":"10.1590\/1516-4446-2013-1139","article-title":"Animal models of anxiety disorders and stress","volume":"35","author":"Campos","year":"2013","journal-title":"Braz. J. Psychiatry"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"495","DOI":"10.31887\/DCNS.2011.13.4\/tsteimer","article-title":"Animal models of anxiety disorders in rats and mice: Some conceptual issues","volume":"13","author":"Steimer","year":"2011","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.biopsych.2012.09.021","article-title":"Inflammatory T helper 17 cells promote depression-like behavior in mice","volume":"73","author":"Beurel","year":"2013","journal-title":"Biol. Psychiatry"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.bbi.2017.08.001","article-title":"Th17 cells in depression","volume":"69","author":"Beurel","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.bbr.2014.09.030","article-title":"Dissociation between sickness behavior and emotionality during lipopolysaccharide challenge in lymphocyte deficient Rag2(-\/-) mice","volume":"278","author":"Clark","year":"2015","journal-title":"Behav. Brain Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.bbi.2014.02.001","article-title":"Immune status influences fear and anxiety responses in mice after acute stress exposure","volume":"38","author":"Clark","year":"2014","journal-title":"Brain Behav. Immun."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e280","DOI":"10.1038\/tp.2013.54","article-title":"CD4(+) but not CD8(+) T cells revert the impaired emotional behavior of immunocompromised RAG-1-deficient mice","volume":"3","author":"Rattazzi","year":"2013","journal-title":"Transl. Psychiatry"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1038\/ni.3867","article-title":"Metabolic shift induced by systemic activation of T cells in PD-1-deficient mice perturbs brain monoamines and emotional behavior","volume":"18","author":"Miyajima","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1710-1492-4-1-2","article-title":"Enhancing versus Suppressive Effects of Stress on Immune Function: Implications for Immunoprotection versus Immunopathology","volume":"4","author":"Dhabhar","year":"2008","journal-title":"Allergy Asthma Clin. Immunol."},{"key":"ref_97","first-page":"10","article-title":"The effect of stress on the defense systems","volume":"3","author":"Dragos","year":"2010","journal-title":"J. Med. Life"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1038\/s41467-017-01919-0","article-title":"Mitochondrial dynamics controls anti-tumour innate immunity by regulating CHIP-IRF1 axis stability","volume":"8","author":"Gao","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.4049\/jimmunol.181.3.1673","article-title":"IFN regulatory factor-1 negatively regulates CD4+ CD25+ regulatory T cell differentiation by repressing Foxp3 expression","volume":"181","author":"Fragale","year":"2008","journal-title":"J. Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1189\/jlb.0406246","article-title":"IRF-1 deficiency skews the differentiation of dendritic cells toward plasmacytoid and tolerogenic features","volume":"80","author":"Gabriele","year":"2006","journal-title":"J. Leukoc. Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1002\/ijc.31083","article-title":"Role of interferon regulatory factor 1 in governing Treg depletion, Th1 polarization, inflammasome activation and antitumor efficacy of cyclophosphamide","volume":"142","author":"Buccione","year":"2018","journal-title":"Int. J. Cancer"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1053\/j.gastro.2019.04.027","article-title":"Depression, Antidepressants, and Inflammatory Bowel Disease: Implications for Future Models of Care","volume":"156","author":"Gracie","year":"2019","journal-title":"Gastroenterology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/4\/1186\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:56:54Z","timestamp":1760173014000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/4\/1186"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,11]]},"references-count":102,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["ijms21041186"],"URL":"https:\/\/doi.org\/10.3390\/ijms21041186","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,11]]}}}