The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring
Open accessAbstract
A T cell cause for autism?: The causes of autism spectrum disorder (ASD) are complex and not entirely clear. Alterations in the mother's immune system during pregnancy, especially during key early periods of fetal neurodevelopment, may play a role. Choi et al. provided infectious or inflammatory stimuli to pregnant mice, which resulted in of spring exhibiting behaviors reminiscent of ASD (see the Perspective by Estes and McAllister). A subset of T helper cells that make the cytokine interleukin-17a in the mothers caused cortical defects and associated ASD behaviors in offspring. Therapeutic targeting of interleukin-17a during gestation reduced ASD symptoms in offspring. Science , this issue p. 933 ; see also p. 919
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“MIA can also induce more complex cortical phenotypes such as focal cortical dysplasia [81, 132], similar to those found in ASD [34] (Fig. 7).”
From The ASD Living Biology: from cell proliferation to clinical phenotype (2019) · cites this paper as [132]
In the citing paper
“Also, cytoarchitecture heterogeneity is seen that is characteristic of ASD cases [34, 132].”
From The ASD Living Biology: from cell proliferation to clinical phenotype (2019) · cites this paper as [132]
In the citing paper
“The Choi and colleagues [132, 81] MIA ASD mouse model study showed that the same fetal MIA perturbation of littermates causes patches of focal cortical dysplasia that have marked heterogeneity, analogous to heterogeneity found in cortex in unrelated individual ASD cases postmortem [34] (Fig. 7).”
From The ASD Living Biology: from cell proliferation to clinical phenotype (2019) · cites this paper as [132]
In the citing paper
“treatment of the anti-IL-17 antibody 2 days after MIA induction saw rescue of some phenotypes, such as USV calls and marble burying, but not others, including interaction deficits”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Choi et al, 2016
In the citing paper
“Given that IL-23 induces IL-17 and the importance of IL-17 for inducing the MIA model of autism (Choi et al, 2016)”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Choi et al, 2016
In the citing paper
“blocking key pathways prevents MIA-induced neural and behavioral abnormalities in ASD model systems.32”
From Maternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder (2018) · cites this paper as [32]
In the citing paper
“MIA alters proliferation of cortical neural progenitor cells, laminar allocation of neurons, increased cortical thickness, increased cell density and patches of cortical dysplasia.32, 38, 42”
From Maternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder (2018) · cites this paper as [32]
In the citing paper
“Increased systemic IL-17 during pregnancy leads to development of autism-like behaviors in pup offspring (Choi et al., 2016), which can also be regulated by maternal microbiota (Kim et al., 2017).”
From The IL-17 Family of Cytokines in Health and Disease (2019) · cites this paper as Choi et al., 2016
In the citing paper
“The implicated cytokine pathways include, and not limited to, IL-5, IL-15, IL-17, IL-17a, IL-10, IL-1b, TNF-α, TGF-β1 and IFNγ [12, 18, 65, 66].”
From Gut microbiota changes in children with autism spectrum disorder: a systematic review (2020) · cites this paper as [66]
In the citing paper
“Alterations of the host immune responses by gut microbiota are closely linked to ASD-related symptoms.”
From Gut microbiota changes in children with autism spectrum disorder: a systematic review (2020) · cites this paper as [66]
In the citing paper
“A number of biomarkers that could connect to microbial profiles also have been identified in ASD, including alterations in serotonin levels, IL1β, and IL6.35, 44, 45, 46, 47”
From Distinct Microbiome-Neuroimmune Signatures Correlate With Functional Abdominal Pain in Children With Autism Spectrum Disorder (2017) · cites this paper as [35]
In the citing paper
“Abnormal behaviors have also been reported in the absence of microbiota, including decreased anxiety-like behavior in the elevated plus maze21.”
From Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons (2020) · cites this paper as [21]
In the citing paper
“Alleviated anxiety-like behavior has been previously linked to the lack of microbiota21.”
From Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons (2020) · cites this paper as [21]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Ivanov, I. I., McKenzie, B. S., Zhou, L., Tadokoro, C. E., Lepelley, A., Lafaille, J. J., Cua, D. J., & Littman, D. R. (2006) · Cell · doi:10.1016/j.cell.2006.07.035 · Cited by 5,145
Self-citationInduction of Intestinal Th17 Cells by Segmented Filamentous Bacteria
Ivanov, I. I., Atarashi, K., Manel, N., Brodie, E. L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K. C., Santee, C. A., Lynch, S. V., et al. (2009) · Cell · doi:10.1016/j.cell.2009.09.033 · Cited by 4,554
Self-citationHsiao, E. Y., McBride, S. W., Hsien, S., Sharon, G., Hyde, E. R., McCue, T., Codelli, J. A., Chow, J., Reisman, S. E., Petrosino, J. F., et al. (2013) · Cell · doi:10.1016/j.cell.2013.11.024 · Cited by 3,283 · cited 1×
“Some studies have reported reduced USV calls upon MIA (8, 31), but these opposite effects may reflect differences in methodological approaches, including dose and number of exposures to poly(I:C) as well as timing of poly(I:C) administration.”
BackgroundNeuronal subtype specification in the cerebral cortex
Molyneaux, B. J., Arlotta, P., Menezes, J. R. L., & Macklis, J. D. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2151 · Cited by 1,704 · cited 1×
“5 as well as in the adult brain using antibodies specific for proteins expressed in the cortex in a layer-specific manner (25): Special AT-rich sequencebinding protein 2 (SATB2) (26), T-brain-1 (TBR1) (27), and chicken ovalbumin upstream promoter transcription factor-interacting protein 2 (CTIP2) (28).”
BackgroundMaternal Immune Activation Alters Fetal Brain Development through Interleukin-6
Smith, S. E. P., Li, J., Garbett, K., Mirnics, K., & Patterson, P. H. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2178-07.2007 · Cited by 1,605 · cited 6×
“3C), consistent with previous studies (7, 29).”
BackgroundResultInfluentialManel, N., Unutmaz, D., & Littman, D. R. (2008) · Nature Immunology · doi:10.1038/ni.1610 · Cited by 1,328
Self-citationFunctional Specialization of Interleukin-17 Family Members
Iwakura, Y., Ishigame, H., Saijo, S., & Nakae, S. (2011) · Immunity · doi:10.1016/j.immuni.2011.02.012 · Cited by 1,289 · cited 1×
“To determine if IL-17a acts on receptors in the mother or the fetus to induce the MIA phenotype, we injected poly(I:C) into IL-17Ra WT, HET or KO mothers that had been bred to IL-17Ra WT or HET males (39).”
MethodEnglund, C., Fink, A., Lau, C., Pham, D., Daza, R. A. M., Bulfone, A., Kowalczyk, T., & Hevner, R. F. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2899-04.2005 · Cited by 1,261 · cited 12×
“Co nt an tiIL -1 7a PBS Poly(I:C) Co nt an tiIL -1 7a 0 500 1000 1500 2000 To ta l d is ta nc e m ov ed ( cm ) 2500 0 100 200 300 400 U S V in de x Co nt an ti- IL -1 7a PBS Poly(I:C) **** ** Co nt an ti- IL -1 7a 0 20 40 60 80 % In te ra ct io n 100 Social Inanimate ** * ** Co nt an ti- IL -1 7a PBS Poly(I:C) Co nt a…”
BackgroundInfluentialPeñagarikano, O., Abrahams, B. S., Herman, E. I., Winden, K. D., Gdalyahu, A., Dong, H., Sonnenblick, L. I., Gruver, R., Almajano, J., Bragin, A., et al. (2011) · Cell · doi:10.1016/j.cell.2011.08.040 · Cited by 1,075 · cited 1×
“Furthermore it is worthwhile to note that the loss of certain genes that induce ASD-like phenotypes were also found with defects in cortical lamination (41, 42).”
BackgroundMaternal Infection Requiring Hospitalization During Pregnancy and Autism Spectrum Disorders
Atladóttir, H. Ó., Thorsen, P., Østergaard, L., Schendel, D. E., Lemcke, S., Abdallah, M., & Parner, E. T. (2010) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-010-1006-y · Cited by 916
Cited by
Sorted by citations
Interactions between the microbiota, immune and nervous systems in health and disease
Fung, T. C., Olson, C. A., & Hsiao, E. Y. (2017) · Nature Neuroscience · doi:10.1038/nn.4476 · Cited by 1,900
Dysbiosis and the immune system
Levy, M., Kolodziejczyk, A. A., Thaiss, C. A., & Elinav, E. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.7 · Cited by 1,769
The central nervous system and the gut microbiome
Sharon, G., Sampson, T. R., Geschwind, D. H., & Mazmanian, S. K. (2016) · Cell · doi:10.1016/j.cell.2016.10.027 · Cited by 1,513
The IL-17 Family of Cytokines in Health and Disease
McGeachy, M. J., Cua, D. J., & Gaffen, S. L. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.021 · Cited by 1,443
“Increased systemic IL-17 during pregnancy leads to development of autism-like behaviors in pup offspring (Choi et al., 2016), which can also be regulated by maternal microbiota (Kim et al.”
BackgroundMaternal immune activation: Implications for neuropsychiatric disorders
Estes, M. L., & McAllister, A. K. (2016) · Science · doi:10.1126/science.aag3194 · Cited by 1,206
Autism spectrum disorder: Definition, epidemiology, causes, and clinical evaluation
Hodges, H., Fealko, C., & Soares, N. (2020) · Translational Pediatrics · doi:10.21037/tp.2019.09.09 · Cited by 1,127
“Maternal infection or immune activation during pregnancy is another area of interest and may be a potential risk factor according to recent investigations (62-65).”
BackgroundIL-17 and IL-17-producing cells in protection versus pathology
Mills, K. H. G. (2022) · Nature reviews. Immunology · doi:10.1038/s41577-022-00746-9 · Cited by 1,051
The Changing Epidemiology of Autism Spectrum Disorders
Lyall, K., Croen, L., Daniels, J., Fallin, M. D., Ladd-Acosta, C., Lee, B. K., Park, B. Y., Snyder, N. W., Schendel, D., Volk, H., et al. (2017) · Annual Review of Public Health · doi:10.1146/annurev-publhealth-031816-044318 · Cited by 1,011
Maternal immune activation and neuroinflammation in human neurodevelopmental disorders
Han, V. X., Patel, S., Jones, H. F., & Dale, R. C. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00530-8 · Cited by 683
Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring
Kim, S., Kim, H., Yim, Y. S., Ha, S., Atarashi, K., Tan, T. G., Longman, R. S., Honda, K., Littman, D. R., Choi, G. B., et al. (2017) · Nature · doi:10.1038/nature23910 · Cited by 678
“8), and these cortical patches resemble lesions described in brains of patients with autism spectrum disorder 11,12 .”
Self-citationCytokine Regulation and Function in T Cells
Dong, C. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-061020-053702 · Cited by 615
Interferons and Proinflammatory Cytokines in Pregnancy and Fetal Development
Yockey, L. J., & Iwasaki, A. (2018) · Immunity · doi:10.1016/j.immuni.2018.07.017 · Cited by 588
“Thus, the brain is susceptible to developmental disruption by increased expression of type I immune cytokines including type I and type II IFNs, IL-17, and IL-1b (Figure 3).”
BackgroundInfluentialThe Role of the Immune System in Autism Spectrum Disorder
Meltzer, A., & Van de Water, J. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.158 · Cited by 533
Why are pregnant women susceptible to COVID-19? An immunological viewpoint
Liu, H., Wang, L., Zhao, S.-J., Kwak-Kim, J. Y.-H., Mor, G., & Liao, A. (2020) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2020.103122 · Cited by 528
A Metabolite-Triggered Tuft Cell-ILC2 Circuit Drives Small Intestinal Remodeling
Schneider, C., O’Leary, C. E., von Moltke, J., Liang, H.-E., Ang, Q. Y., Turnbaugh, P. J., Radhakrishnan, S., Pellizzon, M., Ma, A., & Locksley, R. M. (2018) · Cell · doi:10.1016/j.cell.2018.05.014 · Cited by 478
“Emerging roles for IL-17 family members in neural networks (Choi et al., 2016), including in nematodes (Chen et al.”
The Meningeal Lymphatic System: A New Player in Neurophysiology
Da Mesquita, S., Fu, Z., & Kipnis, J. (2018) · Neuron · doi:10.1016/j.neuron.2018.09.022 · Cited by 479
Immunoneuropsychiatry — novel perspectives on brain disorders
Pape, K., Tamouza, R., Leboyer, M., & Zipp, F. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0174-4 · Cited by 460
Microglia and early brain development: An intimate journey
Thion, M. S., Ginhoux, F., & Garel, S. (2018) · Science · doi:10.1126/science.aat0474 · Cited by 465
“While it has been proposed that IL-17 could act directly on neurons ( 39 ) , it is also well-established that microglia are perturbed by MIA and could thereby contribute to neuronal dysfunction ( 3, 13, 23, 36 ) .”
Mechanisms governing activity-dependent synaptic pruning in the developing mammalian CNS
Faust, T. E., Gunner, G., & Schafer, D. P. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-021-00507-y · Cited by 477
Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons
Alves de Lima, K., Rustenhoven, J., Da Mesquita, S., Wall, M., Salvador, A. F., Smirnov, I., Martelossi Cebinelli, G., Mamuladze, T., Baker, W., Papadopoulos, Z., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0776-4 · Cited by 416
Neuromodulation by the immune system: a focus on cytokines
Salvador, A. F., de Lima, K. A., & Kipnis, J. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-021-00508-z · Cited by 389
Jiang, H.-Y., Xu, L.-L., Shao, L., Xia, R.-M., Yu, Z.-H., Ling, Z.-X., Yang, F., Deng, M., & Ruan, B. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.06.005 · Cited by 391
Transforming the understanding of brain immunity
Castellani, G., Croese, T., Peralta Ramos, J. M., & Schwartz, M. (2023) · Science · doi:10.1126/science.abo7649 · Cited by 386
“5 offspring has been linked to cortical defects and abnormal behavior inmice (34).”
BackgroundMicroglia Require CD4 T Cells to Complete the Fetal-to-Adult Transition
Pasciuto, E., Burton, O. T., Roca, C. P., Lagou, V., Rajan, W. D., Theys, T., Mancuso, R., Tito, R. Y., Kouser, L., Callaerts-Vegh, Z., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.026 · Cited by 368
“Indeed, IFNa (Blank et al., 2016), IFNg (Dulken et al., 2019; Filiano et al., 2016), tumor necrosis factor alpha (TNF-a) (Stellwagen and Malenka, 2006), interleukin (IL)2 (Petitto et al., 1999), IL-4 (Derecki et al., 2010; Kawahara et al., 2012), IL-13 (Kawahara et al., 2012), and IL-17 (Choi et al., 2016) have all be…”
Aburto, M. R., & Cryan, J. F. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00890-0 · Cited by 407
The microbiota–gut–brain axis and neurodevelopmental disorders
Wang, Q., Yang, Q., & Liu, X. (2023) · Protein & Cell · doi:10.1093/procel/pwad026 · Cited by 429
Kawano, Y., Edwards, M., Huang, Y., Bilate, A. M., Araujo, L. P., Tanoue, T., Atarashi, K., Ladinsky, M. S., Reiner, S. L., Wang, H. H., et al. (2022) · Cell · doi:10.1016/j.cell.2022.08.005 · Cited by 349
“To confirm that the protective effects of SF-HFD are mediated by Th17 cells, we examined RORgt-flox/CD4-Cre animals that specifically lack Th17 cell differentiation (Choi et al., 2016).”
BackgroundMaternal immune activation and autism spectrum disorder: From rodents to nonhuman and human primates
Careaga, M., Murai, T., & Bauman, M. D. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.10.020 · Cited by 348
Alves de Lima, K., Rustenhoven, J., & Kipnis, J. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-102319-103410 · Cited by 348
Beyond a neurotransmitter: The role of serotonin in inflammation and immunity
Wu, H., Denna, T., Storkersen, J., & Gerriets, V. A. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.06.015 · Cited by 357
Meningeal γδ T cell-derived IL-17 controls synaptic plasticity and short-term memory
Ribeiro, M., Brigas, H. C., Temido-Ferreira, M., Pousinha, P. A., Regen, T., Santa, C., Coelho, J. E., Marques-Morgado, I., Valente, C. A., Omenetti, S., et al. (2019) · Science Immunology · doi:10.1126/sciimmunol.aay5199 · Cited by 335
The ASD Living Biology: from cell proliferation to clinical phenotype
Courchesne, E., Pramparo, T., Gazestani, V. H., Lombardo, M. V., Pierce, K., & Lewis, N. E. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0056-y · Cited by 333
“The Choi et al. 132 MIA ASD mouse model study showed that the same fetal MIA perturbation of littermates causes patches of focal cortical dysplasia that have marked heterogeneity, analogous to heterogeneity found in cortex in unrelated individual ASD cases postmortem 34 (Figure 7).”
The Impact of Systemic Inflammation on Neurodevelopment
Jiang, N. M., Cowan, M. N., Moonah, S. N., & Petri, W. A. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.06.008 · Cited by 343
“[16] In vivo; mice Retinoic acid receptor-related orphan nuclear receptor gt (RORgt)-dependent effector T lymphocytes [e.”
InfluentialRisks associated with viral infections during pregnancy
Racicot, K. E., & Mor, G. (2017) · Journal of Clinical Investigation · doi:10.1172/jci87490 · Cited by 323
Mucosal fungi promote gut barrier function and social behavior via Type 17 immunity
Leonardi, I., Gao, I. H., Lin, W.-Y., Allen, M., Li, X. V., Fiers, W. D., De Celie, M. B., Putzel, G. G., Yantiss, R. K., Johncilla, M., et al. (2022) · Cell · doi:10.1016/j.cell.2022.01.017 · Cited by 307
Reversing behavioural abnormalities in mice exposed to maternal inflammation
Shin Yim, Y., Park, A., Berrios, J., Lafourcade, M., Pascual, L. M., Soares, N., Yeon Kim, J., Kim, S., Kim, H., Waisman, A., et al. (2017) · Nature · doi:10.1038/nature23909 · Cited by 303
Self-citationControl of Immunity by the Microbiota
Ansaldo, E., Farley, T. K., & Belkaid, Y. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-093019-112348 · Cited by 309
IL-17a promotes sociability in mouse models of neurodevelopmental disorders
Reed, M. D., Yim, Y. S., Wimmer, R. D., Kim, H., Ryu, C., Welch, G. M., Andina, M., King, H. O., Waisman, A., Halassa, M. M., et al. (2020) · Nature · doi:10.1038/s41586-019-1843-6 · Cited by 274
Self-citationILC3s select microbiota-specific regulatory T cells to establish tolerance in the gut
Lyu, M., Suzuki, H., Kang, L., Gaspal, F., Zhou, W., Goc, J., Zhou, L., Zhou, J., Zhang, W., Bank, J. L. C., et al. (2022) · Nature · doi:10.1038/s41586-022-05141-x · Cited by 302
Neuro-Immune Interactions at Barrier Surfaces
Veiga‐Fernandes, H., & Mucida, D. (2016) · Cell · doi:10.1016/j.cell.2016.04.041 · Cited by 293
Luna, R. A., Oezguen, N., Balderas, M., Venkatachalam, A., Runge, J. K., Versalovic, J., Veenstra-VanderWeele, J., Anderson, G. M., Savidge, T., & Williams, K. C. (2017) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2016.11.008 · Cited by 295
Immune cells and CNS physiology: Microglia and beyond
Norris, G. T., & Kipnis, J. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20180199 · Cited by 274
“Recent publications have documented roles for the CD4 T cell–derived cytokines IL-4 (Derecki et al., 2010), IFN-γ (Filiano et al., 2016), and IL-17 (Choi et al., 2016) in brain function.”
BackgroundInfluentialMaternal Immune Activation and Neuropsychiatric Illness: A Translational Research Perspective
Brown, A. S., & Meyer, U. (2018) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2018.17121311 · Cited by 294
“autism spectrum disorders(4-11) and bipolar disorder(12, 13).”
BackgroundInfluentialWu, K.-Y., Zuo, G.-L., Li, X.-F., Ye, Q., Deng, Y.-Q., Huang, X.-Y., Cao, W.-C., Qin, C.-F., & Luo, Z.-G. (2016) · Cell Research · doi:10.1038/cr.2016.58 · Cited by 283
SARS-CoV-2 Infection and COVID-19 During Pregnancy: A Multidisciplinary Review
Narang, K., Enninga, E. A. L., Gunaratne, M. D. S. K., Ibirogba, E. R., Trad, A. T. A., Elrefaei, A., Theiler, R. N., Ruano, R., Szymanski, L. M., Chakraborty, R., et al. (2020) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2020.05.011 · Cited by 290
Obata, Y., & Pachnis, V. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.07.044 · Cited by 286
Beyond Host Defense: Emerging Functions of the Immune System in Regulating Complex Tissue Physiology
Rankin, L. C., & Artis, D. (2018) · Cell · doi:10.1016/j.cell.2018.03.013 · Cited by 276
Inflammation: A Proposed Intermediary Between Maternal Stress and Offspring Neuropsychiatric Risk
Hantsoo, L., Kornfield, S., Anguera, M. C., & Epperson, C. N. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.08.018 · Cited by 269
Microglia in CNS development: Shaping the brain for the future
Mosser, C., Baptista, S., Arnoux, I., & Audinat, É. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.01.002 · Cited by 289
T cell responses in the central nervous system
Korn, T., & Kallies, A. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2016.144 · Cited by 268
Brain changes in a maternal immune activation model of neurodevelopmental brain disorders
Bergdolt, L., & Dunaevsky, A. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.12.002 · Cited by 281
“IL-17a was elevated in the placenta and maternal serum following immune activation, leading to an increase in IL-17a receptor subunit A (IL-17Ra) in the fetal brain (Choi et al., 2016).”
InfluentialInnate immune dysfunction and neuroinflammation in autism spectrum disorder (ASD)
Hughes, H. K., Moreno, R. J., & Ashwood, P. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2022.12.001 · Cited by 288
McConnell, M. J., Moran, J. V., Abyzov, A., Akbarian, S., Bae, T., Cortes-Ciriano, I., Erwin, J. A., Fasching, L., Flasch, D. A., Freed, D., et al. (2017) · Science · doi:10.1126/science.aal1641 · Cited by 262
Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications
Jiang, C.-C., Lin, L., Long, S., Ke, X., Fukunaga, K., Lu, Y., & Han, F. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01081-0 · Cited by 295
The fetal origins of mental illness
al-Haddad, B. J. S., Oler, E., Armistead, B., Elsayed, N. A., Weinberger, D. R., Bernier, R., Burd, I. D., Kapur, R. P., Jacobsson, B., Wang, C., et al. (2019) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2019.06.013 · Cited by 272
The Role of Microbiota in Infant Health: From Early Life to Adulthood
Yao, Y., Cai, X. T., Ye, Y., Wang, F., Chen, F., & Zheng, C. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.708472 · Cited by 271
Brain borders at the central stage of neuroimmunology
Rustenhoven, J., & Kipnis, J. (2022) · Nature · doi:10.1038/s41586-022-05474-7 · Cited by 253
Targeting peripheral somatosensory neurons to improve tactile-related phenotypes in ASD models
Orefice, L. L., Mosko, J. R., Morency, D. T., Wells, M. F., Tasnim, A., Mozeika, S. M., Ye, M., Chirila, A. M., Emanuel, A. J., Rankin, G., et al. (2019) · Cell · doi:10.1016/j.cell.2019.07.024 · Cited by 247
“5 (Figures 5N, 5O), which is a model of maternal immune activation-induced ASD in rodents (Choi et al., 2016).”
BackgroundAn Overview of Animal Models Related to Schizophrenia
Winship, I. R., Dursun, S. M., Baker, G. B., Balista, P. A., Kandratavicius, L., Maia‐de‐Oliveira, J. P., Hallak, J. E. C., & Howland, J. G. (2018) · The Canadian Journal of Psychiatry · doi:10.1177/0706743718773728 · Cited by 263
Innate immunity at the crossroads of healthy brain maturation and neurodevelopmental disorders
Zengeler, K. E., & Lukens, J. R. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-020-00487-7 · Cited by 264
Immune Dysfunction and Autoimmunity as Pathological Mechanisms in Autism Spectrum Disorders
Hughes, H. K., Ko, E. M., Rose, D. R., & Ashwood, P. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00405 · Cited by 253
“IL-17 blockade was also effective in preventing behavioral abnormalities (Choi et al., 2016; Kim et al., 2017).”
BackgroundNeuro–Immune Cell Units: A New Paradigm in Physiology
Godinho‐Silva, C., Cardoso, F., & Veiga‐Fernandes, H. (2018) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042718-041812 · Cited by 250
Reber, S. O., Siebler, P. H., Donner, N. C., Morton, J. T., Smith, D. G., Kopelman, J. M., Lowe, K. R., Wheeler, K. J., Fox, J. H., Hassell, J. E., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1600324113 · Cited by 233
Neuroinflammation and Oxidative Stress in the Pathogenesis of Autism Spectrum Disorder
Usui, N., Kobayashi, H., & Shimada, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065487 · Cited by 278
“5 Reduced ASD-like behaviors and morphological abnormalities in cortex [38]”
BackgroundInfluentialPotential Role of Gut Microbiota in Induction and Regulation of Innate Immune Memory
Negi, S., Das, D. K., Pahari, S., Nadeem, S., & Agrewala, J. N. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02441 · Cited by 247
“In addition, infections during pregnancy can induce maternal immune activation (MIA), which can lead to the generation of immune cells with “memory” phenotype via epigenomic changes (71, 72).”
BackgroundCytokines as emerging regulators of central nervous system synapses
Zipp, F., Bittner, S., & Schafer, D. P. (2023) · Immunity · doi:10.1016/j.immuni.2023.04.011 · Cited by 257
IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer’s disease
Brigas, H. C., Ribeiro, M. A., Coelho, J. E., Gomes, R., Gómez‐Murcia, V., Carvalho, K., Faivre, É., Costa-Pereira, S., Darrigues, J., de Almeida, A. A., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109574 · Cited by 236
Atopic diseases and inflammation of the brain in the pathogenesis of autism spectrum disorders
Theoharides, T. C., Tsilioni, I., Patel, A., & Doyle, R. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.77 · Cited by 234
The microbiota-immune axis as a central mediator of gut-brain communication
Fung, T. C. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104714 · Cited by 234
Prenatal maternal infection promotes tissue-specific immunity and inflammation in offspring
Lim, A. I., McFadden, T. E., Link, V. M., Han, S., Karlsson, R., Stacy, A., Farley, T. K., Lima-Junior, D. S., Harrison, O. J., Desai, J. V., et al. (2021) · Science · doi:10.1126/science.abf3002 · Cited by 231
“IL-6 has been previously linked to various biological outcomes in the context of pregnancy, including gestational disorders (32).”
BackgroundRose, D. R., Yang, H., Serena, G., Sturgeon, C., Ma, B., Careaga, M., Hughes, H. K., Angkustsiri, K., Rose, M., Hertz-Picciotto, I., et al. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.03.025 · Cited by 227
AIM2 inflammasome surveillance of DNA damage shapes neurodevelopment
Lammert, C. R., Frost, E. L., Bellinger, C. E., Bolte, A. C., McKee, C. A., Hurt, M. E., Paysour, M. J., Ennerfelt, H. E., & Lukens, J. R. (2020) · Nature · doi:10.1038/s41586-020-2174-3 · Cited by 223
The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders
Hughes, H. K., Rose, D., & Ashwood, P. (2018) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-018-0887-6 · Cited by 225
The function of gut microbiota in immune-related neurological disorders: a review
Sittipo, P., Choi, J., Lee, S., & Lee, Y. K. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02510-1 · Cited by 221
“Many studies demonstrated that an alteration of the gut microbiome during pregnancy leads to ASD in offspring and this effect is mediated by immune response modulation [138, 153].”
BackgroundNeurodevelopmental Resilience and Susceptibility to Maternal Immune Activation
Meyer, U. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2019.08.001 · Cited by 230
Blum, H. E. (2017) · Advances in Medical Sciences · doi:10.1016/j.advms.2017.04.005 · Cited by 246
Prenatal fever and autism risk
Hornig, M., Bresnahan, M. A., Che, X., Schultz, A. F., Ukaigwe, J. E., Eddy, M. L., Hirtz, D., Gunnes, N., Lie, K. K., Magnus, P., et al. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.119 · Cited by 222
Neuroimmune circuits in inter-organ communication
Huh, J. R., & Veiga‐Fernandes, H. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0247-z · Cited by 216
Self-citationDysbiosis of microbiome and probiotic treatment in a genetic model of autism spectrum disorders
Tabouy, L., Getselter, D., Ziv, O., Karpuj, M., Tabouy, T., Lukic, I., Maayouf, R., Werbner, N., Ben-Amram, H., Nuriel-Ohayon, M., et al. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.05.015 · Cited by 214
The role of GABAergic signalling in neurodevelopmental disorders
Tang, X., Jaenisch, R., & Sur, M. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-021-00443-x · Cited by 221
Gumusoglu, S. B., & Stevens, H. E. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.08.008 · Cited by 216
Lombardo, M. V., Moon, H. M., Su, J., Palmer, T. D., Courchesne, E., & Pramparo, T. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.15 · Cited by 201
Maternal inflammation and its ramifications on fetal neurodevelopment
Kwon, H., Choi, G. B., & Huh, J. R. (2022) · Trends in Immunology · doi:10.1016/j.it.2022.01.007 · Cited by 204
Self-citationImmune dysfunction and neuroinflammation in autism spectrum disorder
Bjørklund, G., Saad, K., Chirumbolo, S., Kern, J. K., Geier, D. A., Geier, M. R., & Urbina, M. A. (2016) · Acta Neurobiologiae Experimentalis · doi:10.21307/ane-2017-025 · Cited by 188
Microglia: Immune Regulators of Neurodevelopment
Cowan, M. N., & Petri, W. A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02576 · Cited by 197
“Recently, a strong link between maternal Th17derived IL-17 and the MIA phenotype in offspring has been established (25).”
BackgroundInflammatory memory and tissue adaptation in sickness and in health
Naik, S., & Fuchs, E. V. (2022) · Nature · doi:10.1038/s41586-022-04919-3 · Cited by 188
Beurel, E., & Lowell, J. A. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2017.08.001 · Cited by 187
Critical Neurotransmitters in the Neuroimmune Network
Hodo, T., de Aquino, M. T. P., Shimamoto, A., & Shanker, A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01869 · Cited by 192
“Maternal TH17 cells have been shown to induce structural alterations in the cortex and autism-like behavioral abnormalities (77).”
BackgroundNicotine reverses hypofrontality in animal models of addiction and schizophrenia
Koukouli, F., Rooy, M., Tziotis, D., Sailor, K. A., O’Neill, H. C., Levenga, J., Witte, M., Nilges, M., Changeux, J., Hoeffer, C. A., et al. (2017) · Nature Medicine · doi:10.1038/nm.4274 · Cited by 191
Self-citationTowards an Immunophenotype of Schizophrenia: Progress, Potential Mechanisms, and Future Directions
Miller, B. J., & Goldsmith, D. R. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.211 · Cited by 182
Role of the Immune System in the Development of the Central Nervous System
Morimoto, K., & Nakajima, K. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00916 · Cited by 190
Dash, S., Syed, Y. A., & Khan, M. R. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.880544 · Cited by 193
“IL-6 and IL-17 may bring on the poly (I: C), an immune stimulant in the MIA model, which affects the fetal brain (Choi et al., 2016; S. E. P.; Smith et al., 2007).”
BackgroundThe microbiota, immunoregulation, and mental health: implications for public health
Lowry, C. A., Smith, D. G., Siebler, P. H., Schmidt, D., Stamper, C. E., Hassell, J. E., Yamashita, P. S., Fox, J. H., Reber, S. O., Brenner, L. A., et al. (2016) · Current Environmental Health Reports · doi:10.1007/s40572-016-0100-5 · Cited by 172
Zawadzka, A., Cieślik, M., & Adamczyk, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111516 · Cited by 197
“demonstrated that maternal CD4+ T cells expressing RORγt are essential for the ASD-like phenotype to occur in offspring [64].”
BackgroundInfluentialMaternal immune activation in neurodevelopmental disorders
Solek, C. M., Farooqi, N., Verly, M., Lim, T. K., & Ruthazer, E. S. (2018) · Developmental Dynamics · doi:10.1002/dvdy.24612 · Cited by 168
“Maternal IL-17a signaling was found to be both necessary and sufficient to produce neurobehavioral deficits in a mouse model of MIA (Choi et al., 2016).”
BackgroundResultInfluentialMicroglia and Neurodevelopmental Disorders
Lukens, J. R., & Eyo, U. B. (2022) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-110920-023056 · Cited by 171
Immune Dysregulation in Autism Spectrum Disorder: What Do We Know about It?
Robinson-Agramonte, M. D. L. A., Noris García, E., Fraga Guerra, J., Vega Hurtado, Y., Antonucci, N., Semprún-Hernández, N., Schultz, S., & Siniscalco, D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23063033 · Cited by 176
The contribution of the gut microbiome to neurodevelopment and neuropsychiatric disorders
Warner, B. B. (2018) · Pediatric Research · doi:10.1038/s41390-018-0191-9 · Cited by 171
Neurodevelopmental Outcomes of Prenatal Preeclampsia Exposure
Gumusoglu, S. B., Chilukuri, A. S. S., Santillan, D. A., Santillan, M. K., & Stevens, H. E. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.02.003 · Cited by 175
“, embryonic cortical dysplasia and laminar organization defects, autism-relevant behavior changes) in mice via IL-17dependent mechanisms [98], suggesting that IL-17 dysregulation in preeclampsia may underlie this risk in clinical populations.”
BackgroundInfections and Pregnancy: Effects on Maternal and Child Health
Kumar, M., Saadaoui, M., & Khodor, S. A. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.873253 · Cited by 173
“…2003; Chavan et al., 2016) IL-17 • Modulates the production of other pro-inflammatory cytokines • Overexpression can mediate abnormal brain development (Choi et al., 2016) TNF-a • Key cytokine to modulate responses against infection • TNF-a concentrations increase as gestation progresses albeit…”
Background
Metadata
- Authors
- Choi, G. B., Yim, Y. S., Wong, H., Kim, S., Kim, H., Kim, S. V., Hoeffer, C. A., Littman, D. R., & Huh, J. R.
- Affiliations
- McGovern Institute for Brain Research (US)
- University of Colorado Boulder (US)
- University of Massachusetts Chan Medical School (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Choi, Gloria B.
- Yim, Yeong S.
- Wong, Helen
- Hoeffer, Charles A.
- Littman, Dan R.
- Huh, Jun R.
- ORCID
- Venue
- Science
- Published
- 2016-02-26
- Volume
- 351
- Issue
- 6276
- Pages
- 933-939
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4782964
- OpenAlex
- W2253802357
- Cited by
- 1,214
- References
- 47
- Citations by year
- 2026: 108 · 2025: 137 · 2024: 147 · 2023: 123 · 2022: 155 · 2021: 136 · 2020: 109 · 2019: 82 · 2018: 97 · 2017: 65 · 2016: 50
- FWCI
- 62.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- PMC
- Funders
- Simons Foundation Autism Research Initiative
- Simons Foundation to the Simons Center for the Social Brain at Massachusetts Institute of Technology
- Robert Buxton
- National Research Foundation of Korea (MEST-35B-2011-1-E00012, NRF-2014R1A1A1006089)
- Crohn’s and Colitis Foundation of America (329388)
- Smith Family Foundation
- Searle Scholars Program
- Alzheimer's Association (MNIRGDP-12-258900)
- Brain and Behavior Research Foundation (NARSAD) (21069)
- NIH (F31NS083277, R00DK091508, R01NS086933)
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- maternal immune activation, autism spectrum disorder, IL-17A, RORγt, Th17 cells, maternal viral infection, autism-like behavior, fetal brain, prenatal inflammation
- MeSH terms
- Autism Spectrum Disorder, Retinoic Acid Receptor gamma, Animals, Behavior, Animal, Behavioral Symptoms, Cerebral Cortex, Female, Male, Maternal-Fetal Exchange, Mutation, Phenotype, Pregnancy, Prenatal Exposure Delayed Effects, RNA, Messenger, Signal Transduction, Receptors, Retinoic Acid, Antibodies, Blocking, Interleukin-17, Mice, Nuclear Receptor Subfamily 1, Group F, Member 3, Th17 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
