Autoimmune aspects of neurodegenerative and psychiatric diseases: A template for innovative therapy

Frontiers in Psychiatry

Volumn 8, Issue APR, 2017, Pages

  de Haan, Peter ^a   Klein, Hans C ^b   't Hart, Bert A ^c  

^a Amarna Therapeutics   (Netherlands)

^b UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^c BIOMEDICAL PRIMATE RESEARCH CENTRE   (Netherlands)

Author keywords

Chronic inflammation; Immune tolerance; Neurodegenerative disease; Psychiatric disease; Reverse vaccine; Self antigen; Viral vector

Indexed keywords

ANTIINFLAMMATORY AGENT; AUTOANTIGEN; DOPAMINE; GLUTAMIC ACID; HISTAMINE; IMMUNOSUPPRESSIVE AGENT; NEUROTRANSMITTER; VIRUS VECTOR;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; ANXIETY; ATTENTION DEFICIT DISORDER; AUTISM; AUTOIMMUNE DISEASE; AUTOIMMUNITY; BEHAVIOR; BRAIN DAMAGE; CHOLINERGIC SYSTEM; DEGENERATIVE DISEASE; DEMENTIA; DEPRESSION; DISEASE COURSE; DOPAMINERGIC SYSTEM; ENCEPHALITIS; EXPERIMENTAL THERAPY; HEALTH CARE COST; HUMAN; HUNTINGTON CHOREA; IMMUNE RESPONSE; IMMUNE SYSTEM; IMMUNOTHERAPY; INCIDENCE; INFLAMMATORY DISEASE; LIFE EXPECTANCY; LYMPHOCYTIC INFILTRATION; MENTAL DISEASE; MORTALITY; MULTIPLE SCLEROSIS; NONHUMAN; PARKINSON DISEASE; PATHOGENESIS; QUALITY OF LIFE; REVIEW; REWARD DEFICIENCY SYNDROME; SCHIZOPHRENIA; SEROTONINERGIC SYSTEM; TIC;

EID: 85018263297     PISSN: None     EISSN: 16640640     Source Type: Journal    
DOI: 10.3389/fpsyt.2017.00046     Document Type: Review

References (144)

1. Tang D, Kang R, Coyne CB, Zeh HJ, Lotze MT. PAMPs and DAMPs: signal 0s that spur autophagy and immunity. Immunol Rev (2012) 249:158-75. doi: 10.1111/j.1600-065X.2012.01146.x
2. Lehtimaki S, Lahesmaa R. Regulatory T cells control immune responses through their non-redundant tissue specific features. Front Immunol (2013) 4:e294. doi:10.3389/fimmu.2013.00294
3. Poon IK, Lucas CD, Rossi AG, Ravichandran KS. Apoptotic cell clearance: basic biology and therapeutic potential. Nat Rev Immunol (2012) 14:166-80. doi:10.1038/nri3607
4. Broz P, Dixit VM. Inflammasomes: mechanism of assembly, regulation and signaling. Nat Rev Immunol (2016) 16:407-20. doi:10.1038/nri.2016.58
5. Nolz JC, Starbeck-Miller GR, Harty JT. Naive, effector and memory CD8 T-cell trafficking: parallels and distinctions. Immunotherapy (2011) 3:1223-33. doi:10.2217/imt.11.100
6. Leavy O. Cell death: pathways for cross-priming. Nat Rev Immunol (2015) 15:725. doi:10.1038/nri3933
7. Hart BA, van Kooyk Y. Yin-Yang regulation of autoimmunity by DCs. Trends Immunol (2004) 25:353-9. doi:10.1016/j.it.2004.04.006
8. Neumann H, Medana IM, Bauer J, Lassmann H. Cytotoxic T lymphocytes in autoimmune and degenerative CNS diseases. Trends Neurosci (2002) 2:313-9. doi:10.1016/S0166-2236(02)02154-9
9. Melzer N, Meuth SG, Wiendl H. CD8+ T cells and neuronal damage: direct and collateral mechanisms of cytotoxicity and impaired electrical excitability. FASEB J (2009) 23:3659-73. doi:10.1096/fj.09-136200
10. Amor S, Puentes F, Baker D, van der Valk P. Inflammation in neurodegenerative diseases. Immunology (2010) 129:154-69. doi:10.1111/j.1365-2567.2009.03225.x
11. Mills KH. TLR-dependent T cell activation in autoimmunity. Nat Rev Immunol (2011) 11:807-22. doi:10.1038/nri3095
12. Nathan C, Ding A. Nonresolving inflammation. Cell (2010) 140:871-82. doi:10.1016/j.cell.2010.02.029
13. Najjar S, Pearlman DM, Alper K, Najjar A, Devinsky O. Neuroinflammation and psychiatric illness. J Neuroinflammation (2013) 10:43. doi:10.1186/1742-2094-10-43
14. Rioux JD, Abbas AK. Paths to understanding the genetic basis of autoimmune disease. Nature (2005) 435:584-9. doi:10.1038/nature03723
15. Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol (2016) 15:391-404. doi:10.1016/S1474-4422(15)00401-9
16. Irani SR, Vincent A. Autoimmune encephalitis-new awareness, challenging questions. Discov Med (2011) 11:449-58.
17. Selmi C, Rose NR. Current trends in autoimmunity and the nervous system. J Autoimmun (2016) 75:20-9. doi:10.1016/j.jaut.2016.08.005
18. Panzara MA, Gussoni E, Begovich AB, Murray RS, Zang YQ, Appel SH, et al. T cell receptor BV gene rearrangements in the spinal cords and cerebrospinal fluid of patients with amyotrophic lateral sclerosis. Neurobiol Dis (1999) 6:392-405. doi:10.1006/nbdi.1999.0252
19. Schneider-Hohendorf T, Mohan H, Bien CG, Breuer J, Becker A, Görlich D, et al. CD8(+) T-cell pathogenicity in Rasmussen encephalitis elucidated by large-scale T-cell receptor sequencing. Nat Commun (2016) 7:11153. doi:10.1038/ncomms11153
20. Bechter K. Updating the mild encephalitis hypothesis of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry (2013) 42:71-91. doi:10.1016/j.pnpbp.2012.06.019
21. Steinman L. Immunology of relapse and remission in multiple sclerosis. Annu Rev Immunol (2014) 32:257-81. doi:10.1146/annurev-immunol-032713-120227
22. Hohlfeld R, Dornmair K, Meinl E, Wekerle H. The search for the target antigens of multiple sclerosis, part 2: CD8+ T cells, B cells, and antibodies in the focus of reverse-translational research. Lancet Neurol (2016) 15:317-31. doi:10.1016/S1474-4422(15)00313-0
23. Miller SD, Karpus WJ, Davidson TS. Experimental autoimmune encephalomyelitis in the mouse. Curr Protoc Immunol (2010). doi:10.1002/0471142735.im1501s88
24. McManus RM, Mills KH, Lynch MA. T cells-protective or pathogenic in Alzheimer's disease? J Neuroimmune Pharmacol (2015) 10:547-60. doi:10.1007/s11481-015-9612-2
25. Lehrer S, Rheinstein PH. Is Alzheimer's disease autoimmune inflammation of the brain that can be treated with nasal nonsteroidal anti-inflammatory drugs? Am J Alzheimers Dis Other Demen (2015) 30:225-7. doi:10.1177/1533317514545478
26. Lueg G, Gross CC, Lohmann H, Johnen A, Kemmling A, Deppe M, et al. Clinical relevance of specific T-cell activation in the blood and cerebrospinal fluid of patients with mild Alzheimer's disease. Neurobiol Aging (2015) 36:81-9. doi:10.1016/j.neurobiolaging.2014.08.008
27. Chapman J, Feldon J, Alroy G, Michaelson DM. Immunization of rats with cholinergic neurons induces behavioral deficits. J Neural Transplant (1989) 1:63-76. doi:10.1155/NP.1989.63
28. Michaelson DM, Dubovik V, Faigon M, Eilam D, Feldon J. Decreased density of forebrain cholinergic neurons and disintegration of the spatial organization of behavior in experimental autoimmune dementia (EAD). Ann N Y Acad Sci (1993) 695:244-8. doi:10.1111/j.1749-6632.1993.tb23061.x
29. Chapman J, Alroy G, Weiss Z, Faigon M, Feldon J, Michaelson DM. Anti-neuronal antibodies similar to those found in Alzheimer's disease induce memory dysfunction in rats. Neuroscience (1991) 40:297-305. doi:10.1016/0306-4522(91)90121-4
30. Bartos A, Fialová L, Svarcová J, Ripova D. Patients with Alzheimer disease have elevated intrathecal synthesis of antibodies against tau protein and heavy neurofilament. J Neuroimmunol (2012) 252:100-5. doi:10.1016/j.jneuroim.2012.08.001
31. Lampson LA, Kushner PD, Sobel RA. Major histocompatibility complex antigen expression in the affected tissues in amyotrophic lateral sclerosis. Ann Neurol (1990) 28:365-72. doi:10.1002/ana.410280311
32. Troost D, van den Oord JJ, de Jong VJM. Immunohistochemical characterization of the inflammatory infiltrate in amyotrophic lateral sclerosis. Neuropathol Appl Neurobiol (1990) 16:401-10. doi:10.1111/j.1365-2990.1990.tb01276.x
33. Kawamata T, Akiyama H, Yamada T, McGeer PL. Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue. Am J Pathol (1992) 140:691-707.
34. Engelhardt JI, Tajti J, Appel SH. Lymphocytic infiltrates in the spinal cord in amyotrophic lateral sclerosis. Arch Neurol (1993) 50:30-6. doi:10.1001/archneur.1993.00540010026013
35. Pagani MR, Gonzalez LE, Uchitel OD. Autoimmunity in amyotrophic lateral sclerosis: past and present. Neurol Res Int (2011) 2011:497080. doi:10.1155/2011/497080
36. Engelhardt JI, Appel SH, Killian JM. Experimental autoimmune motoneuron disease. Ann Neurol (1989) 26:368-76. doi:10.1002/ana.410260310
37. Huizinga R, Heijmans N, Schubert P, Gschmeissner S, Hart BA, Herrmann H, et al. Immunization with neurofilament light protein induces spastic paresis and axonal degeneration in Biozzi ABH mice. J Neuropathol Exp Neurol (2007) 66:295-304. doi:10.1097/nen.0b013e318040ad5c
38. Niebroj-Dobosz I, Dziewulska D, Janik P. Auto-antibodies against proteins of spinal cord cells in cerebrospinal fluid of patients with amyotrophic lateral sclerosis (ALS). Folia Neuropathol (2006) 44:191-6.
39. Fialová L, Svarcová J, Bartos A, Ridzon P, Malbohan I, Keller O, et al. Cerebrospinal fluid and serum antibodies against neurofilaments in patients with amyotrophic lateral sclerosis. Eur J Neurol (2010) 17:562-6. doi:10.1111/j.1468-1331.2009.02853.x
40. Puentes F, Topping J, Kuhle J, van der Star BJ, Douiri A, Giovannoni G, et al. Immune reactivity to neurofilament proteins in the clinical staging of amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry (2014) 85:274-8. doi:10.1136/jnnp-2013-305494
41. Goines P, van de Water J. The immune system's role in the biology of autism. Curr Opin Neurol (2010) 23:111-7. doi:10.1097/WCO.0b013e3283373514
42. Depino AM. Peripheral and central inflammation in autism spectrum disorders. Mol Cell Neurosci (2013) 53:69-76. doi:10.1016/j.mcn.2012.10.003
43. McDougle CJ, Landino SM, Vahabzadeh A, O'Rourke J, Zurcher NR, Finger BC, et al. Toward an immune-mediated subtype of autism spectrum disorder. Brain Res (2015) 1617:72-92. doi:10.1016/j.brainres.2014.09.048
44. Wang JQ, McGinty JF. Intrastriatal injection of a muscarinic receptor agonist and antagonist regulates striatal neuropeptide mRNA expression in normal and amphetamine-treated rats. Brain Res (1997) 748:62-70. doi:10.1016/S0006-8993(96)01244-9
45. Amodeo DA, Yi J, Sweeney JA, Ragozzino ME. Oxotremorine treatment reduces repetitive behaviors in BTBR T+ tf/J mice. Front Synaptic Neurosci (2014) 6:17. doi:10.3389/fnsyn.2014.00017
46. Karvat G, Kimchi T. Acetylcholine elevation relieves cognitive rigidity and social deficiency in a mouse model of autism. Neuropsychopharmacology (2014) 39:831-40. doi:10.1038/npp.2013.274
47. Aliane V, Pérez S, Bohren Y, Deniau JM, Kemel ML. Key role of striatal cholinergic interneurons in processes leading to arrest of motor stereotypies. Brain (2011) 134:110-8. doi:10.1093/brain/awq285
48. Crotti A, Glass CK. The choreography of neuroinflammation in Huntington's disease. Trends Immunol (2015) 36:364-73. doi:10.1016/j.it.2015.04.007
49. McGeer PL, Itagaki S, Boyes BE, McGeer EG. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains. Neurology (1988) 38:1285-91. doi:10.1212/WNL.38.8.1285
50. Brochard V, Combadière B, Prigent A, Laouar Y, Perrin A, Beray-Berthat V, et al. Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest (2009) 119:182-92. doi:10.1172/JCI36470
51. Hirsch EC, Hunot S. Neuroinflammation in Parkinson's disease: a target for neuroprotection? Lancet Neurol (2009) 8:382-97. doi:10.1016/S1474-4422(09)70062-6
52. Abramsky O, Litvin Y. Autoimmune response to dopamine-receptor as a possible mechanism in the pathogenesis of Parkinson's disease and schizophrenia. Perspect Biol Med (1978) 22:104-14.
53. Le WD, Engelhardt J, Xie WJ, Schneider L, Smith RG, Appel SH. Experimental autoimmune nigral damage in guinea pigs. J Neuroimmunol (1995) 57:45-53. doi:10.1016/0165-5728(94)00160-P
54. Appel SH, Le WD, Tajti J, Haverkamp LJ, Engelhardt JI. Nigral damage and dopaminergic hypofunction in mesencephalon-immunized guinea pigs. Ann Neurol (1992) 32:494-501. doi:10.1002/ana.410320403
55. Chen MK, Kuwabara H, Zhou Y, Adams RJ, Brasic JR, McGlothan JL, et al. VMAT2 and dopamine neuron loss in a primate model of Parkinson's disease. J Neurochem (2008) 105:78-90. doi:10.1111/j.1471-4159.2007.05108.x
56. Pifl C, Rajput A, Reither H, Blesa J, Cavada C, Obeso JA, et al. Is Parkinson's disease a vesicular dopamine storage disorder? Evidence from a study in isolated synaptic vesicles of human and nonhuman primate striatum. J Neurosci (2014) 34:8210-8. doi:10.1523/JNEUROSCI.5456-13.2014
57. Kurkowska-Jastrzebska I, Wronska A, Kohutnicka M, Czlonkowski A, Czlonkowska A. MHC class II positive microglia and lymphocytic infiltration are present in the substantia nigra and striatum in mouse model of Parkinson's disease. Acta Neurobiol Exp (Wars) (1999) 59:1-8.
58. Takahashi N, Miner LL, Sora I, Ujike H, Revay RS, Kostic V, et al. VMAT2 knockout mice: heterozygotes display reduced amphetamine-conditioned reward, enhanced amphetamine locomotion, and enhanced MPTP toxicity. Proc Natl Acad Sci U S A (1997) 94:9938-43. doi:10.1073/pnas.94.18.9938
59. Lohr KM, Bernstein AI, Stout KA, Dunn AR, Lazo CR, Alter SP, et al. Increased vesicular monoamine transporter enhances dopamine release and opposes Parkinson disease-related neurodegeneration in vivo. Proc Natl Acad Sci U S A (2014) 111:9977-82. doi:10.1073/pnas.1402134111
60. Taylor TN, Caudle WM, Miller GW. VMAT2-deficient mice display nigral and extranigral pathology and motor and nonmotor symptoms of Parkinson's disease. Parkinsons Dis (2011) 2011:124165. doi:10.4061/2011/124165
61. Ceylan MF, Sener S, Bayraktar AC, Kavutcu M. Changes in oxidative stress and cellular immunity serum markers in attention-deficit/hyperactivity disorder. Psychiatry Clin Neurosci (2012) 66:220-6. doi:10.1111/j.1440-1819.2012.02330.x
62. Silk TJ, Vance A, Rinehart N, Bradshaw JL, Cunnington R. White-matter abnormalities in attention deficit hyperactivity disorder: a diffusion tensor imaging study. Hum Brain Mapp (2009) 30:2757-65. doi:10.1002/hbm.20703
63. Dickstein SG, Bannon K, Castellanos FX, Milham MP. The neural correlates of attention deficit hyperactivity disorder: an ALE meta-analysis. J Child Psychol Psychiatry (2006) 47:1051-62. doi:10.1111/j.1469-7610.2006.01671.x
64. Adriani W, Koot S, Columba-Cabezas S, Romano E, Travaglini D, van den Bos R, et al. Immunization with DAT fragments is associated with long-term striatal impairment, hyperactivity and reduced cognitive flexibility in mice. Behav Brain Funct (2012) 8:54. doi:10.1186/1744-9081-8-54
65. Zhuang X, Oosting RS, Jones SR, Gainetdinov RR, Miller GW, Caron MG, et al. Hyperactivity and impaired response habituation in hyperdopaminergic mice. Proc Natl Acad Sci U S A (2001) 98:1982-7. doi:10.1073/pnas.98.4.1982
66. Giros B, Jaber M, Jones SR, Wightman RM, Caron MG. Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature (1996) 379:606-12. doi:10.1038/379606a0
67. Gainetdinov RR, Wetsel WC, Jones SR, Levin ED, Jaber M, Caron MG. Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity. Science (1999) 283:397-401. doi:10.1126/science.283.5400.397
68. Hall FS, Sora I, Hen R, Uhl GR. Serotonin/dopamine interactions in a hyperactive mouse: reduced serotonin receptor 1B activity reverses effects of dopamine transporter knockout. PLoS One (2014) 9:e115009. doi:10.1371/journal.pone.0115009
69. Giana G, Romano E, Porfirio MC, D'Ambrosio R, Giovinazzo S, Troianiello M, et al. Detection of auto-antibodies to DAT in the serum: interactions with DAT genotype and psycho-stimulant therapy for ADHD. J Neuroimmunol (2015) 278:212-22. doi:10.1016/j.jneuroim.2014.11.008
70. Rajkowska G, Miguel-Hidalgo JJ, Wei J, Dilley G, Pittman SD, Meltzer HY, et al. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry (1999) 45:1085-98. doi:10.1016/S0006-3223(99)00041-4
71. Fowler JS, Volkow ND, Kassed CA, Chang L. Imaging the addicted human brain. Sci Pract Perspect (2007) 3:4-16. doi:10.1151/spp07324
72. Menzies L, Chamberlain SR, Laird AR, Thelen SM, Sahakian BJ, Bullmore ET. Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited. Neurosci Biobehav Rev (2008) 32:525-49. doi:10.1016/j.neubiorev.2007.09.005
73. Schiepek G, Tominschek I, Karch S, Mulert C, Pogarell O. Neuroimaging and the neurobiology of obsessive-compulsive disorder. Psychother Psychosom Med Psychol (2007) 57:379-94. doi:10.1055/s-2006-952021
74. Saxena S, Brody AL, Schwartz JM, Baxter LR. Neuroimaging and frontal-subcortical circuitry in obsessive-compulsive disorder. Br J Psychiatry Suppl (1998) 35:26-37.
75. Graybiel AM, Rauch SL. Toward a neurobiology of obsessive-compulsive disorder. Neuron (2000) 28:343-7. doi:10.1016/S0896-6273(00)00113-6
76. Bhattacharyya S, Khanna S, Chakrabarty K, Mahadevan A, Christopher R, Shankar SK. Anti-brain autoantibodies and altered excitatory neurotransmitters in obsessive-compulsive disorder. Neuropsychopharmacology (2009) 34:2489-96. doi:10.1038/npp.2009.77
77. Dale RC, Heyman I, Giovannoni G, Church AW. Incidence of anti-brain antibodies in children with obsessive-compulsive disorder. Br J Psychiatry (2005) 187:314-9. doi:10.1192/bjp.187.4.314
78. Blum K, Chen AL, Giordano J, Borsten J, Chen TJ, Hauser M, et al. The addictive brain: all roads lead to dopamine. J Psychoactive Drugs (2012) 44:134-43. doi:10.1080/02791072.2012.685407
79. Volkow ND, Fowler JS, Wang GJ. Imaging studies on the role of dopamine in cocaine reinforcement and addiction in humans. J Psychopharmacol (1999) 13:337-45. doi:10.1177/026988119901300406
80. Heber D, Carpenter CL. Addictive genes and the relationship to obesity and inflammation. Mol Neurobiol (2011) 44:160-5. doi:10.1007/s12035-011-8180-6
81. Johnson PM, Kenny PJ. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci (2010) 13:635-41. doi:10.1038/nn.2519
82. Bello EP, Mateo Y, Gelman DM, Noaín D, Shin JH, Low MJ, et al. Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors. Nat Neurosci (2011) 14:1033-8. doi:10.1038/nn.2862
83. Thanos PK, Michaelides M, Umegaki H, Volkow ND. D2R DNA transfer into the nucleus accumbens attenuates cocaine self-administration in rats. Synapse (2008) 62:481-6. doi:10.1002/syn.20523
84. Pilla M, Perachon S, Sautel F, Garrido F, Mann A, Wermuth CG, et al. Selective inhibition of cocaine-seeking behaviour by a partial dopamine D3 receptor agonist. Nature (1999) 400:371-5. doi:10.1038/22560
85. Lammers CH, Diaz J, Schwartz JC, Sokoloff P. Selective increase of dopamine D3 receptor gene expression as a common effect of chronic antidepressant treatments. Mol Psychiatry (2000) 5:378-88. doi:10.1038/sj.mp.4000756
86. Schwartz JC, Diaz J, Pilon C, Sokoloff P. Possible implications of the dopamine D(3) receptor in schizophrenia and in antipsychotic drug actions. Brain Res Brain Res Rev (2000) 31:277-87. doi:10.1016/S0165-0173(99)00043-0
87. Berridge KC, Aldridge JW. Super-stereotypy I: enhancement of a complex movement sequence by systemic dopamine D1 agonists. Synapse (2000) 37:194-204. doi:10.1002/1098-2396(20000901)37:3<205::AID-SYN4>3.0.CO;2-A
88. Xu D, Miller SD, Koh S. Immune mechanisms in epileptogenesis. Front Cell Neurosci (2013) 7:195. doi:10.3389/fncel.2013.00195
89. Vezzani A, French J, Bartfai T, Baram TZ. The role of inflammation in epilepsy. Nat Rev Neurol (2011) 7:31-40. doi:10.1038/nrneurol.2010.178
90. Toledano M, Pittock SJ. Autoimmune epilepsy. Semin Neurol (2015) 35:245-58. doi:10.1055/s-0035-1552625
91. Zhou X, Hollern D, Liao J, Andrechek E, Wang H. NMDA receptor-mediated excitotoxicity depends on the coactivation of synaptic and extrasynaptic receptors. Cell Death Dis (2013) 4:e560. doi:10.1038/cddis.2013.82
92. Furman M. Seizure initiation and propagation in the pilocarpine rat model of temporal lobe epilepsy. J Neurosci (2013) 33:16409-11. doi:10.1523/JNEUROSCI.3687-13.2013
93. Mantegazza R, Bernasconi P, Baggi F, Spreafico R, Ragona F, Antozzi C. Antibodies against GluR3 peptides are not specific for Rasmussen's encephalitis but are also present in epilepsy patients with severe, early onset disease and intractable seizures. J Neuroimmunol (2002) 131:179-85. doi:10.1016/S0165-5728(02)00261-8
94. Bien CG, Bauer J, Deckwerth TL, Wiendl H, Deckert M, Wiestler OD, et al. Destruction of neurons by cytotoxic T cells: a new pathogenic mechanism in Rasmussen's encephalitis. Ann Neurol (2002) 51:311-8. doi:10.1002/ana.10100
95. Boer K, Jansen F, Nellist M, Redeker S, van den Ouweland AM, Spliet WG, et al. Inflammatory processes in cortical tubers and subependymal giant cell tumors of tuberous sclerosis complex. Epilepsy Res (2008) 78:7-21. doi:10.1016/j.eplepsyres.2007.10.002
96. Schwab N, Bien CG, Waschbisch A, Becker A, Vince GH, Dornmair K, et al. CD8+ T-cell clones dominate brain infiltrates in Rasmussen encephalitis and persist in the periphery. Brain (2009) 132:1236-46. doi:10.1093/brain/awp003
97. Moldrich RX, Chapman AG, De Sarro G, Meldrum BS. Glutamate metabotropic receptors as targets for drug therapy in epilepsy. Eur J Pharmacol (2003) 476:3-16. doi:10.1016/S0014-2999(03)02149-6
98. Twyman RE, Gahring LC, Spiess J, Rogers SW. Glutamate receptor antibodies activate a subset of receptors and reveal an agonist binding site. Neuron (1995) 14:755-62. doi:10.1016/0896-6273(95)90219-8
99. Rogers SW, Andrews PI, Gahring LC, Whisenand T, Cauley K, Crain B, et al. Autoantibodies to glutamate receptor GluR3 in Rasmussen's encephalitis. Science (1994) 265:648-51. doi:10.1126/science.8036512
100. Bloomfield PS, Selvaraj S, Veronese M, Rizzo G, Bertoldo A, Owen DR, et al. Microglial activity in people at ultra high risk of psychosis and in schizophrenia: an [(11)C]PBR28 PET brain imaging study. Am J Psychiatry (2016) 173:44-52. doi:10.1176/appi.ajp.2015.14101358
101. Busse S, Busse M, Schiltz K, Bielau H, Gos T, Brisch R, et al. Different distribution patterns of lymphocytes and microglia in the hippocampus of patients with residual versus paranoid schizophrenia: further evidence for disease course-related immune alterations? Brain Behav Immun (2012) 26:1273-9. doi:10.1016/j.bbi.2012.08.005
102. Pasternak O, Westin CF, Bouix S, Seidman LJ, Goldstein JM, Woo TU, et al. Excessive extracellular volume reveals a neurodegenerative pattern in schizophrenia onset. J Neurosci (2012) 32:17365-72. doi:10.1523/JNEUROSCI.2904-12.2012
103. Arnone D, McKie S, Elliott R, Juhasz G, Thomas EJ, Downey D, et al. State-dependent changes in hippocampal grey matter in depression. Mol Psychiatry (2013) 18:1265-72. doi:10.1038/mp.2012.150
104. Cannon TD, Chung Y, He G, Sun D, Jacobson A, van Erp TG, et al. Progressive reduction in cortical thickness as psychosis develops: a multisite longitudinal neuroimaging study of youth at elevated clinical risk. Biol Psychiatry (2015) 77:147-57. doi:10.1016/j.biopsych.2014.05.023
105. Debnath M. Adaptive immunity in schizophrenia: functional implications of T cells in the etiology, course and treatment. J Neuroimmune Pharmacol (2015) 10:610-9. doi:10.1007/s11481-015-9626-9
106. Doorduin J, de Vries EF, Willemsen AT, de Groot JC, Dierckx RA, Klein HC. Neuroinflammation in schizophrenia-related psychosis: a PET study. J Nucl Med (2009) 50:1801-7. doi:10.2967/jnumed.109.066647
107. Mohn AR, Gainetdinov RR, Caron MG, Koller BH. Mice with reduced NMDA receptor expression display behaviors related to schizophrenia. Cell (1999) 98:427-36. doi:10.1016/S0092-8674(00)81972-8
108. Bygrave AM, Masiulis S, Nicholson E, Berkemann M, Barkus C, Sprengel R, et al. Knockout of NMDA-receptors from parvalbumin interneurons sensitizes to schizophrenia-related deficits induced by MK-801. Transl Psychiatry (2016) 6:e778. doi:10.1038/tp.2016.44
109. Klein HC, Doorduin J, de Witte L, de Vries EFJ. Microglia activation, herpes infection, and NMDA receptor inhibition: common pathways to psychosis? In: Müller N, Myint A-M, Schwarz MJ, editors. Immunology and Psychiatry, Current Topics in Neurotoxicity. (Vol. 8), Switzerland: Springer International Publishing (2015). p. 243-54.
110. Irani SR, Vincent A. NMDA receptor antibody encephalitis. Curr Neurol Neurosci Rep (2011) 11:298-304. doi:10.1007/s11910-011-0186-y
111. Hoekstra PJ, Kallenberg CG, Korf J, Minderaa RB. Is Tourette's syndrome an autoimmune disease? Mol Psychiatry (2002) 7:437-45. doi:10.1038/sj.mp.4000972
112. Leckman JF, Katsovich L, Kawikova I, Lin H, Zhang H, Krönig H, et al. Increased serum levels of interleukin-12 and tumor necrosis factor-alpha in Tourette's syndrome. Biol Psychiatry (2005) 57:667-73. doi:10.1016/j.biopsych.2004.12.004
113. Castellan Baldan L, Williams KA, Gallezot JD, Pogorelov V, Rapanelli M, Crowley M, et al. Histidine decarboxylase deficiency causes tourette syndrome: parallel findings in humans and mice. Neuron (2014) 81:77-90. doi:10.1016/j.neuron.2013.10.052
114. Kononoff Vanhanen J, Nuutinen S, Tuominen M, Panula P. Histamine H3 receptor regulates sensorimotor gating and dopaminergic signaling in the striatum. J Pharmacol Exp Ther (2016) 357:264-72. doi:10.1124/jpet.115.230771
115. Berk M, Williams LJ, Jacka FN, O'Neil A, Pasco JA, Moylan S, et al. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med (2013) 11:200. doi:10.1186/1741-7015-11-200
116. Setiawan E, Wilson AA, Mizrahi R, Rusjan PM, Miler L, Rajkowska G, et al. Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes. JAMA Psychiatry (2015) 72:268-75. doi:10.1001/jamapsychiatry.2014.2427
117. Rajkowska G, Miguel-Hidalgo JJ, Dubey P, Stockmeier CA, Krishnan KR. Prominent reduction in pyramidal neurons density in the orbitofrontal cortex of elderly depressed patients. Biol Psychiatry (2005) 58:297-306. doi:10.1016/j.biopsych.2005.04.013
118. Ressler KJ, Mayberg HS. Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic. Nat Neurosci (2007) 10:1116-24. doi:10.1038/nn1944
119. Cheng W, Rolls ET, Qiu J, Liu W, Tang Y, Huang CC, et al. Medial reward and lateral non-reward orbitofrontal cortex circuits change in opposite directions in depression. Brain (2016) 139:aww255. doi:10.1093/brain/aww255
120. Torres-Platas SG, Cruceanu C, Chen GG, Turecki G, Mechawar N. Evidence for increased microglial priming and macrophage recruitment in the dorsal anterior cingulate white matter of depressed suicides. Brain Behav Immun (2014) 42:50-9. doi:10.1016/j.bbi.2014.05.007
121. Miller AH, Raison CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol (2016) 16:22-34. doi:10.1038/nri.2015.5
122. Albert PR, Vahid-Ansari F, Luckhart C. Serotonin-prefrontal cortical circuitry in anxiety and depression phenotypes: pivotal role of pre-and post-synaptic 5-HT1A receptor expression. Front Behav Neurosci (2014) 8:199. doi:10.3389/fnbeh.2014.00199
123. Urani A, Chourbaji S, Gass P. Mutant mouse models of depression: candidate genes and current mouse lines. Neurosci Biobehav Rev (2005) 29:805-28. doi:10.1016/j.neubiorev.2005.03.020
124. Olivier JD, van der Hart MG, van Swelm RP, Dederen PJ, Homberg JR, Cremers T, et al. A study in male and female 5-HT transporter knockout rats: an animal model for anxiety and depression disorders. Neuroscience (2008) 152:573-84. doi:10.1016/j.neuroscience.2007.12.032
125. Jakubovski E, Varigonda AL, Freemantle N, Taylor MJ, Bloch MH. Systematic review and meta-analysis: dose-response relationship of selective serotonin reuptake inhibitors in major depressive disorder. Am J Psychiatry (2016) 173:174-83. doi:10.1176/appi.ajp.2015.15030331
126. Chen HX, Jin ZL, Zhang LM, Xue R, Xu XD, Zhao N, et al. Antidepressant-like activity of YL-0919: a novel combined selective serotonin reuptake inhibitor and 5-HT1A receptor agonist. PLoS One (2013) 8:e83271. doi:10.1371/journal.pone.0083271
127. Rosenblat JD, Brietzke E, Mansur RB, Maruschak NA, Lee Y, McIntyre RS. Inflammation as a neurobiological substrate of cognitive impairment in bipolar disorder: evidence, pathophysiology and treatment implications. J Affect Disord (2015) 188:149-59. doi:10.1016/j.jad.2015.08.058
128. Salim S, Chugh G, Asghar M. Inflammation in anxiety. Adv Protein Chem Struct Biol (2012) 88:1-25. doi:10.1016/B978-0-12-398314-5.00001-5
129. Marcinkiewcz CA, Mazzone CM, D'Agostino G, Halladay LR, Hardaway JA, DiBerto JF, et al. Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala. Nature (2016) 537:97-101. doi:10.1038/nature19318
130. Murray CJL, Lopez ADL. Alternative projections of mortality and disability by cause 1990-2020: global burden of disease study. Lancet (1997) 349:1498-504. doi:10.1016/S0140-6736(96)07492-2
131. Kessler RC, Aguilar-Gaxiola S, Alonso J, Chatterji S, Lee S, Ustün TB. The WHO world mental health (WMH) surveys. Psychiatrie (Stuttg) (2009) 6:5-9.
132. Collins PY, Patel V, Joestl SS, March D, Insel TR, Daar AS, et al. Grand challenges in global mental health. Nature (2011) 475:27-30. doi:10.1038/475027a
133. Keller WR, Kum LM, Wehring HJ, Koola MM, Buchanan RW, Kelly DL. A review of anti-inflammatory agents for symptoms of schizophrenia. J Psychopharmacol (2013) 27:337-42. doi:10.1177/0269881112467089
134. Cappellano G, Woldetsadik AD, Orilieri E, Shivakumar Y, Rizzi M, Carniato F, et al. Subcutaneous inverse vaccination with PLGA particles loaded with a MOG peptide and IL-10 decreases the severity of experimental autoimmune encephalomyelitis. Vaccine (2014) 32:5681-9. doi:10.1016/j.vaccine.2014.08.016
135. Jurynczyk M, Walczak A, Jurewicz A, Jesionek-Kupnicka D, Szczepanik M, Selmaj K. Immune regulation of multiple sclerosis by transdermally applied myelin peptides. Ann Neurol (2010) 68:593-601. doi:10.1002/ana.22219
136. Yuan B, Zhao L, Fu F, Liu Y, Lin C, Wu X, et al. A novel nanoparticle containing MOG peptide with BTLA induces T cell tolerance and prevents multiple sclerosis. Mol Immunol (2014) 57:93-9. doi:10.1016/j.molimm.2013.08.006
137. Carambia A, Freund B, Schwinge D, Bruns OT, Salmen SC, Ittrich H, et al. Nanoparticle-based autoantigen delivery to Treg-inducing liver sinusoidal endothelial cells enables control of autoimmunity in mice. J Hepatol (2015) 62:1349-56. doi:10.1016/j.jhep.2015.01.006
138. Harrison LC. Insulin-specific vaccination for type 1 diabetes: a step closer? Hum Vaccin Immunother (2012) 8:834-7. doi:10.4161/hv.19673
139. Elsner M, Terbish T, Jörns A, Naujok O, Wedekind D, Hedrich HJ, et al. Reversal of diabetes through gene therapy of diabetic rats by hepatic insulin expression via lentiviral transduction. Mol Ther (2012) 20:918-26. doi:10.1038/mt.2012.8
140. Lüth S, Huber S, Schramm C, Buch T, Zander S, Stadelmann C, et al. Ectopic expression of neural autoantigen in mouse liver suppresses experimental autoimmune neuroinflammation by inducing antigen-specific Tregs. J Clin Invest (2008) 118:3403-10. doi:10.1172/JCI32132
141. Eneljung T, Tengvall S, Jirholt P, Henningsson L, Holmdahl R, Gustafsson K, et al. Antigen-specific gene therapy after immunisation reduces the severity of collagen-induced arthritis. Clin Dev Immunol (2013) 2013:345092. doi:10.1155/2013/345092
142. Gjertsson I, Laurie KL, Devitt J, Howe SJ, Thrasher AJ, Holmdahl R, et al. Tolerance induction using lentiviral gene delivery delays onset and severity of collagen II arthritis. Mol Ther (2009) 17:632-40. doi:10.1038/mt.2009.299
143. Sack BK, Herzog RW, Terhorst C, Markusic DM. Development of gene transfer for induction of antigen-specific tolerance. Mol Ther Methods Clin Dev (2014) 1:14013. doi:10.1038/mtm.2014.13
144. Zhang P, Sun B, Osada T, Rodriguiz R, Yang XY, Luo X, et al. Immunodominant liver-specific expression suppresses transgene-directed immune responses in murine pompe disease. Hum Gene Ther (2012) 23:460-72. doi:10.1089/hum.2011.063