Antigen-presenting innate lymphoid cells orchestrate neuroinflammation

  • 1.

    Ota, K. et al. T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Nature 346, 183–187 (1990).

    CAS 
    PubMed 
    ADS 

    Google Scholar 

  • 2.

    Dendrou, C. A., Fugger, L. & Friese, M. A. Immunopathology of multiple sclerosis. Nat. Rev. Immunol. 15, 545–558 (2015).

    CAS 
    PubMed 

    Google Scholar 

  • 3.

    Togo, T. et al. Occurrence of T cells in the brain of Alzheimer’s disease and other neurological diseases. J. Neuroimmunol. 124, 83–92 (2002).

    CAS 
    PubMed 

    Google Scholar 

  • 4.

    Monsonego, A. et al. Increased T cell reactivity to amyloid β protein in older humans and patients with Alzheimer disease. J. Clin. Invest. 112, 415–422 (2003).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 5.

    Sulzer, D. et al. T cells from patients with Parkinson’s disease recognize α-synuclein peptides. Nature 546, 656–661 (2017).

    CAS 
    PubMed 
    PubMed Central 
    ADS 

    Google Scholar 

  • 6.

    Lindestam Arlehamn, C. S. et al. alpha-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson’s disease. Nat. Commun. 11, 1875 (2020).

    CAS 
    PubMed 
    PubMed Central 
    ADS 

    Google Scholar 

  • 7.

    Lincoln, M. R. et al. A predominant role for the HLA class II region in the association of the MHC region with multiple sclerosis. Nat. Genet. 37, 1108–1112 (2005).

    CAS 
    PubMed 

    Google Scholar 

  • 8.

    Hamza, T. H. et al. Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease. Nat. Genet. 42, 781–785 (2010).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 9.

    Jansen, I. E. et al. Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk. Nat. Genet. 51, 404–413 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 10.

    Nalls, M. A. et al. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease. Nat. Genet. 46, 989–993 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 11.

    Fallis, R. J., Raine, C. S. & McFarlin, D. E. Chronic relapsing experimental allergic encephalomyelitis in SJL mice following the adoptive transfer of an epitope-specific T cell line. J. Neuroimmunol. 22, 93–105 (1989).

    CAS 
    PubMed 

    Google Scholar 

  • 12.

    Brochard, V. et al. Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J. Clin. Invest. 119, 182–192 (2009).

    CAS 
    PubMed 

    Google Scholar 

  • 13.

    Browne, T. C. et al. IFN-γ production by amyloid β-specific Th1 cells promotes microglial activation and increases plaque burden in a mouse model of Alzheimer’s disease. J. Immunol. 190, 2241–2251 (2013).

    CAS 
    PubMed 

    Google Scholar 

  • 14.

    Lodygin, D. et al. β-Synuclein-reactive T cells induce autoimmune CNS grey matter degeneration. Nature 566, 503–508 (2019).

    CAS 
    PubMed 
    ADS 

    Google Scholar 

  • 15.

    Dulken, B. W. et al. Single-cell analysis reveals T cell infiltration in old neurogenic niches. Nature 571, 205–210 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 16.

    Vivier, E. et al. Innate lymphoid cells: 10 years on. Cell 174, 1054–1066 (2018).

    CAS 
    PubMed 

    Google Scholar 

  • 17.

    Sonnenberg, G. F. & Hepworth, M. R. Functional interactions between innate lymphoid cells and adaptive immunity. Nat. Rev. Immunol. 19, 599–613 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 18.

    Mair, F. & Becher, B. Thy1+ Sca1+ innate lymphoid cells infiltrate the CNS during autoimmune inflammation, but do not contribute to disease development. Eur. J. Immunol. 44, 37–45 (2014).

    CAS 
    PubMed 

    Google Scholar 

  • 19.

    Hatfield, J. K. & Brown, M. A. Group 3 innate lymphoid cells accumulate and exhibit disease-induced activation in the meninges in EAE. Cell. Immunol. 297, 69–79 (2015).

    CAS 
    PubMed 

    Google Scholar 

  • 20.

    Kwong, B. et al. T-bet-dependent NKp46+ innate lymphoid cells regulate the onset of TH17-induced neuroinflammation. Nat. Immunol. 18, 1117–1127 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 21.

    Yamano, T. et al. Aire-expressing ILC3-like cells in the lymph node display potent APC features. J. Exp. Med. 216, 1027–1037 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 22.

    Gasteiger, G., Fan, X., Dikiy, S., Lee, S. Y. & Rudensky, A. Y. Tissue residency of innate lymphoid cells in lymphoid and nonlymphoid organs. Science 350, 981–985 (2015).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 23.

    Takeshita, Y. & Ransohoff, R. M. Inflammatory cell trafficking across the blood–brain barrier: chemokine regulation and in vitro models. Immunol. Rev. 248, 228–239 (2012).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 24.

    Perry, J. S. et al. Inhibition of LTi cell development by CD25 blockade is associated with decreased intrathecal inflammation in multiple sclerosis. Sci. Transl. Med. 4, 145ra106 (2012).

    PubMed 

    Google Scholar 

  • 25.

    Lin, Y. C. et al. Daclizumab reverses intrathecal immune cell abnormalities in multiple sclerosis. Ann. Clin. Transl. Neurol. 2, 445–455 (2015).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 26.

    Degn, M. et al. Increased prevalence of lymphoid tissue inducer cells in the cerebrospinal fluid of patients with early multiple sclerosis. Mult. Scler. 22, 1013–1020 (2016).

    CAS 
    PubMed 

    Google Scholar 

  • 27.

    Serafini, B. et al. RORγt expression and lymphoid neogenesis in the brain of patients with secondary progressive multiple sclerosis. J. Neuropathol. Exp. Neurol. 75, 877–888 (2016).

    CAS 
    PubMed 

    Google Scholar 

  • 28.

    Hepworth, M. R. et al. Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria. Nature 498, 113–117 (2013).

    CAS 
    PubMed 
    PubMed Central 
    ADS 

    Google Scholar 

  • 29.

    Hepworth, M. R. et al. Immune tolerance. Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4+ T cells. Science 348, 1031–1035 (2015).

    CAS 
    PubMed 
    PubMed Central 
    ADS 

    Google Scholar 

  • 30.

    von Burg, N. et al. Activated group 3 innate lymphoid cells promote T-cell-mediated immune responses. Proc. Natl Acad. Sci. USA 111, 12835–12840 (2014).

    ADS 

    Google Scholar 

  • 31.

    Ting, J. P. & Trowsdale, J. Genetic control of MHC class II expression. Cell 109, S21–S33, (2002).

    CAS 
    PubMed 

    Google Scholar 

  • 32.

    Schroder, K., Hertzog, P. J., Ravasi, T. & Hume, D. A. Interferon-γ: an overview of signals, mechanisms and functions. J. Leukoc. Biol. 75, 163–189 (2004).

    CAS 
    PubMed 

    Google Scholar 

  • 33.

    Bryant, P. W., Lennon-Dumenil, A. M., Fiebiger, E., Lagaudriere-Gesbert, C. & Ploegh, H. L. Proteolysis and antigen presentation by MHC class II molecules. Adv. Immunol. 80, 71–114 (2002).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 34.

    Zhang, Q. & Vignali, D. A. Co-stimulatory and co-inhibitory pathways in autoimmunity. Immunity 44, 1034–1051 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 35.

    Lee, J. Y. et al. Serum amyloid A proteins induce pathogenic Th17 cells and promote inflammatory disease. Cell 180, 79–91 (2020).

    CAS 
    PubMed 

    Google Scholar 

  • 36.

    Koda, T. et al. Sema4A is implicated in the acceleration of Th17 cell-mediated neuroinflammation in the effector phase. J. Neuroinflammation 17, 82 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 37.

    Hur, E. M. et al. Osteopontin-induced relapse and progression of autoimmune brain disease through enhanced survival of activated T cells. Nat. Immunol. 8, 74–83 (2007).

    CAS 
    PubMed 

    Google Scholar 

  • 38.

    Giles, D. A., Duncker, P. C., Wilkinson, N. M., Washnock-Schmid, J. M. & Segal, B. M. CNS-resident classical DCs play a critical role in CNS autoimmune disease. J. Clin. Invest. 128, 5322–5334 (2018).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 39.

    Mundt, S. et al. Conventional DCs sample and present myelin antigens in the healthy CNS and allow parenchymal T cell entry to initiate neuroinflammation. Sci. Immunol. 4, eaau8380 (2019).

    CAS 
    PubMed 

    Google Scholar 

  • 40.

    Korn, T. & Kallies, A. T cell responses in the central nervous system. Nat. Rev. Immunol. 17, 179–194 (2017).

    CAS 
    PubMed 

    Google Scholar 

  • 41.

    Waisman, A. & Johann, L. Antigen-presenting cell diversity for T cell reactivation in central nervous system autoimmunity. J. Mol. Med. 96, 1279–1292 (2018).

    CAS 
    PubMed 

    Google Scholar 

  • 42.

    Frommer, F. et al. Tolerance without clonal expansion: self-antigen-expressing B cells program self-reactive T cells for future deletion. J. Immunol. 181, 5748–5759 (2008).

    CAS 
    PubMed 

    Google Scholar 

  • 43.

    Buonocore, S. et al. Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology. Nature 464, 1371–1375 (2010).

    CAS 
    PubMed 
    PubMed Central 
    ADS 

    Google Scholar 

  • 44.

    Huang, Y. et al. IL-25-responsive, lineage-negative KLRG1hi cells are multipotential ‘inflammatory’ type 2 innate lymphoid cells. Nat. Immunol. 16, 161–169 (2015).

    CAS 
    PubMed 

    Google Scholar 

  • 45.

    Huang, Y. et al. S1P-dependent interorgan trafficking of group 2 innate lymphoid cells supports host defense. Science 359, 114–119 (2018).

    CAS 
    PubMed 
    PubMed Central 
    ADS 

    Google Scholar 

  • 46.

    Montaldo, E. et al. Human RORγt+CD34+ cells are lineage-specified progenitors of group 3 RORγt+ innate lymphoid cells. Immunity 41, 988–1000 (2014).

    CAS 
    PubMed 

    Google Scholar 

  • 47.

    Lim, A. I. et al. Systemic human ILC precursors provide a substrate for tissue ILC differentiation. Cell 168, 1086–1100 (2017).

    CAS 
    PubMed 

    Google Scholar 

  • 48.

    Scoville, S. D. et al. A progenitor cell expressing transcription factor RORγt generates all human innate lymphoid cell subsets. Immunity 44, 1140–1150 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 49.

    Jordao, M. J. C. et al. Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation. Science 363, eaat7554 (2019).

    CAS 
    PubMed 

    Google Scholar 

  • 50.

    Hashimoto, K., Joshi, S. K. & Koni, P. A. A conditional null allele of the major histocompatibility IA-beta chain gene. Genesis 32, 152–153 (2002).

    CAS 
    PubMed 

    Google Scholar 

  • 51.

    Bettelli, E. et al. Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis. J. Exp. Med. 197, 1073–1081 (2003).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 52.

    Srinivas, S. et al. Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus. BMC Dev. Biol 1, 4 (2001).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 53.

    Lee, P. P. et al. A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival. Immunity 15, 763–774 (2001).

    CAS 
    PubMed 

    Google Scholar 

  • 54.

    Dobes, J. et al. A novel conditional Aire allele enables cell-specific ablation of the immune tolerance regulator Aire. Eur. J. Immunol. 48, 546–548 (2018).

    CAS 
    PubMed 

    Google Scholar 

  • 55.

    Hirota, K. et al. Fate mapping of IL-17-producing T cells in inflammatory responses. Nat. Immunol. 12, 255–263 (2011).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 56.

    Ahlfors, H. et al. IL-22 fate reporter reveals origin and control of IL-22 production in homeostasis and infection. J. Immunol. 193, 4602–4613 (2014).

    CAS 
    PubMed 

    Google Scholar 

  • 57.

    Lochner, M. et al. In vivo equilibrium of proinflammatory IL-17+ and regulatory IL-10+ Foxp3+ RORγ t+ T cells. J. Exp. Med. 205, 1381–1393 (2008).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 58.

    Croxford, A. L., Kurschus, F. C. & Waisman, A. Cutting edge: an IL-17F-CreEYFP reporter mouse allows fate mapping of Th17 cells. J. Immunol. 182, 1237–1241 (2009).

    CAS 
    PubMed 

    Google Scholar 

  • 59.

    Polman, C. H. et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann. Neurol. 69, 292–302 (2011).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 60.

    Miller, S. D., Karpus, W. J. & Davidson, T. S. Experimental autoimmune encephalomyelitis in the mouse. Curr. Protoc. Immunol. 88, 15.1.1–15.1.20 (2010).

    Google Scholar 

  • 61.

    Lee, Y. et al. Induction and molecular signature of pathogenic TH17 cells. Nat. Immunol. 13, 991–999 (2012).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 62.

    Kamran, P. et al. Parabiosis in mice: a detailed protocol. J. Vis. Exp. 80, e50556 (2013).

    Google Scholar 

  • 63.

    Edgar, R. C. Search and clustering orders of magnitude faster than BLAST. Bioinformatics 26, 2460–2461 (2010).

    CAS 

    Google Scholar 

  • 64.

    Edgar, R. C. SINTAX: a simple non-Bayesian taxonomy classifier for 16S and ITS sequences. Preprint at https://doi.org/10.1101/074161 (2016).

  • 65.

    Cole, J. R. et al. Ribosomal Database Project: data and tools for high throughput rRNA analysis. Nucleic Acids Res. 42, D633–D642 (2014).

    CAS 
    PubMed 

    Google Scholar 

  • 66.

    McMurdie, P. J. & Holmes, S. phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS ONE 8, e61217 (2013).

    CAS 
    PubMed 
    PubMed Central 
    ADS 

    Google Scholar 

  • 67.

    Louveau, A., Filiano, A. J. & Kipnis, J. Meningeal whole mount preparation and characterization of neural cells by flow cytometry. Curr. Protoc. Immunol. 121, e50 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Leave a Reply

    Your email address will not be published. Required fields are marked *