Rosenblum, M. D., Remedios, K. A. & Abbas, A. K. Mechanisms of human autoimmunity. J. Clin. Invest. 125, 2228–2233 https://doi.org/10.1172/jci78088 (2015).
Google Scholar
Goodnow, C. C., Sprent, J., de St Groth, B. F. & Vinuesa, C. G. Cellular and genetic mechanisms of self tolerance and autoimmunity. Nature 435, 590–597 https://doi.org/10.1038/nature03724 (2005).
Google Scholar
Pisetsky, D. S. Pathogenesis of autoimmune disease. Nat. Rev. Nephrol. 19, 509–524 https://doi.org/10.1038/s41581-023-00720-1 (2023).
Google Scholar
Sumida, T. S., Cheru, N. T. & Hafler, D. A. The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases. Nat. Rev. Immunol. 24, 503–517 https://doi.org/10.1038/s41577-024-00994-x (2024).
Google Scholar
Billingham, R. E. Transplantation immunity evoked by skin homografts and expressed in intact skin. Adv. Biol. Skin 11, 183–198 (1971).
Google Scholar
Paus, R., Nickoloff, B. J. & Ito, T. A. ‘Hairy’ privilege. Trends Immunol. 26, 32–40 https://doi.org/10.1016/j.it.2004.09.014 (2005).
Google Scholar
Reynolds, A. J., Lawrence, C., Cserhalmi-Friedman, P. B., Christiano, A. M. & Jahoda, C. A. B. Trans-gender induction of hair follicles. Nature 402, 33–34 https://doi.org/10.1038/46938 (1999).
Google Scholar
Agudo, J. et al. Quiescent tissue stem cells evade immune surveillance. Immunity 48, 271–285 https://doi.org/10.1016/j.immuni.2018.02.001 (2018).
Google Scholar
Cohen, J. N. et al. Regulatory T cells in skin mediate immune privilege of the hair follicle stem cell niche. Sci. Immunol. 9, eadh0152 https://doi.org/10.1126/sciimmunol.adh0152 (2024).
Google Scholar
Pratt, C. H., King, L. E., Messenger, A. G., Christiano, A. M. & Sundberg, J. P. Alopecia areata. Nat. Rev. Dis. Primers 3, 17011 https://doi.org/10.1038/nrdp.2017.11 (2017).
Google Scholar
Kanti, V., Röwert-Huber, J., Vogt, A. & Blume-Peytavi, U. Cicatricial alopecia. JDDG 16, 435–461 https://doi.org/10.1111/ddg.13498 (2018).
Google Scholar
Sundberg, J. P., Cordy, W. R. & King, L. E. Alopecia areata in aging C3H/HeJ mice. J. Invest. Dermatol. 102, 847–856 https://doi.org/10.1111/1523-1747.ep12382416 (1994).
Google Scholar
Blanpain, C. & Fuchs, E. Epidermal homeostasis: a balancing act of stem cells in the skin. Nat. Rev. Mol. Cell Biol. 10, 207–217 https://doi.org/10.1038/nrm2636 (2009).
Google Scholar
Watt, F. M. & Jensen, K. B. Epidermal stem cell diversity and quiescence. EMBO Mol. Med. 1, 260–267 https://doi.org/10.1002/emmm.200900033 (2009).
Google Scholar
Zhang, B. & Chen, T. Local and systemic mechanisms that control the hair follicle stem cell niche. Nat. Rev. Mol. Cell Biol. 25, 87–100 https://doi.org/10.1038/s41580-023-00662-3 (2024).
Google Scholar
Millar, S. E. Molecular mechanisms regulating hair follicle development. J. Invest. Dermatol. 118, 216–225 https://doi.org/10.1046/j.0022-202x.2001.01670.x (2002).
Google Scholar
Hsu, Y. C. & Fuchs, E. Building and maintaining the skin. Cold Spring Harb. Perspect. Biol. 14, a040840 https://doi.org/10.1101/cshperspect.a040840 (2022).
Müller-Röver, S. et al. A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages. J. Invest. Dermatol. 117, 3–15 https://doi.org/10.1046/j.0022-202x.2001.01377.x (2001).
Google Scholar
Plikus, M. V. & Chuong, C.-M. Macroenvironmental regulation of hair cycling and collective regenerative behavior. Cold Spring Harb. Perspect. Med. 4, a015198 https://doi.org/10.1101/cshperspect.a015198 (2014).
Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M. & Toda, M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 155, 1151–1164 https://doi.org/10.4049/jimmunol.155.3.1151 (1995).
Google Scholar
Fontenot, J. D., Gavin, M. A. & Rudensky, A. Y. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 4, 330–336 https://doi.org/10.1038/ni904 (2003).
Google Scholar
Hori, S., Nomura, T. & Sakaguchi, S. Control of regulatory T cell development by the transcription factor Foxp3. Science 299, 1057–1061 https://doi.org/10.1126/science.1079490 (2003).
Google Scholar
Khattri, R., Cox, T., Yasayko, S.-A. & Ramsdell, F. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat. Immunol. 4, 337–342 https://doi.org/10.1038/ni909 (2003).
Google Scholar
Kim, J. M., Rasmussen, J. P. & Rudensky, A. Y. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat. Immunol. 8, 191–197 https://doi.org/10.1038/ni1428 (2007).
Google Scholar
Ali, N. et al. Regulatory T cells in skin facilitate epithelial stem cell differentiation. Cell 169, 1119–1129 https://doi.org/10.1016/j.cell.2017.05.002 (2017).
Google Scholar
Mandala, S. et al. Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science 296, 346–349 https://doi.org/10.1126/science.1070238 (2002).
Google Scholar
Shwartz, Y. et al. Cell types promoting goosebumps form a niche to regulate hair follicle stem cells. Cell 182, 578–593 https://doi.org/10.1016/j.cell.2020.06.031 (2020).
Google Scholar
Fan, S. M.-Y. et al. External light activates hair follicle stem cells through eyes via an ipRGC–SCN–sympathetic neural pathway. Proc. Natl Acad. Sci. USA 115, E6880–E6889 https://doi.org/10.1073/pnas.1719548115 (2018).
Google Scholar
Schwab, M. E., Javoy-Agid, F. & Agid, Y. Labeled wheat germ agglutinin (WGA) as a new, highly sensitive retrograde tracer in the rat brain hippocampal system. Brain Res. 152, 145–150 https://doi.org/10.1016/0006-8993(78)90140-3 (1978).
Google Scholar
Thoenen, H. & Tranzer, J. P. Chemical sympathectomy by selective destruction of adrenergic nerve endings with 6-hydroxydopamine. Naunyn Schmiedebergs Arch. Pharmakol. Exp. Pathol. 261, 271–288 https://doi.org/10.1007/BF00536990 (1968).
Google Scholar
Madisen, L. et al. A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing. Nat. Neurosci. 15, 793–802 https://doi.org/10.1038/nn.3078 (2012).
Google Scholar
Ulrich-Lai, Y. M. & Herman, J. P. Neural regulation of endocrine and autonomic stress responses. Nat. Rev. Neurosci. 10, 397–409 https://doi.org/10.1038/nrn2647 (2009).
Google Scholar
Zhang, B. et al. Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells. Nature 577, 676–681 https://doi.org/10.1038/s41586-020-1935-3 (2020).
Google Scholar
Boullin, D. J., Costa, E. & Brodie, B. B. Discharge of tritium-labeled guanethidine by sympathetic nerve stimulation as evidence that guanethidine is a false transmitter. Life Sci. 5, 803–808 https://doi.org/10.1016/0024-3205(66)90303-1 (1966).
Google Scholar
Lima-Junior, D. S. et al. Endogenous retroviruses promote homeostatic and inflammatory responses to the microbiota. Cell 184, 3794–3811 https://doi.org/10.1016/j.cell.2021.05.020 (2021).
Google Scholar
Dopkins, N. et al. A field guide to endogenous retrovirus regulatory networks. Mol. Cell 82, 3763–3768 https://doi.org/10.1016/j.molcel.2022.09.011 (2022).
Google Scholar
Dopkins, N. & Nixon, D. F. Activation of human endogenous retroviruses and its physiological consequences. Nat. Rev. Mol. Cell Biol. 25, 212–222 https://doi.org/10.1038/s41580-023-00674-z (2024).
Google Scholar
Stoye, J. P. Studies of endogenous retroviruses reveal a continuing evolutionary saga. Nat. Rev. Microbiol. 10, 395–406 https://doi.org/10.1038/nrmicro2783 (2012).
Google Scholar
Matsui, T. et al. Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET. Nature 464, 927–931 https://doi.org/10.1038/nature08858 (2010).
Google Scholar
Rowe, H. M. et al. KAP1 controls endogenous retroviruses in embryonic stem cells. Nature 463, 237–240 https://doi.org/10.1038/nature08674 (2010).
Google Scholar
Johnson, W. E. Origins and evolutionary consequences of ancient endogenous retroviruses. Nat. Rev. Microbiol. 17, 355–370 https://doi.org/10.1038/s41579-019-0189-2 (2019).
Google Scholar
Martin, J. L., Cao, S., Maldonado, J. O., Zhang, W. & Mansky, L. M. Distinct particle morphologies revealed through comparative parallel analyses of retrovirus-like particles. J. Virol. 90, 8074–8084 https://doi.org/10.1128/jvi.00666-16 (2016).
Google Scholar
Zhang, W., Cao, S., Martin, J. L., Mueller, J. D. & Mansky, L. M. Morphology and ultrastructure of retrovirus particles. AIMS Biophys. 2, 343–369 https://doi.org/10.3934/biophy.2015.3.343 (2015).
Google Scholar
Dewannieux, M. et al. Identification of an infectious progenitor for the multiple-copy HERV-K human endogenous retroelements. Genome Res. 16, 1548–1556 https://doi.org/10.1101/gr.5565706 (2006).
Xu, Z. et al. Anatomically distinct fibroblast subsets determine skin autoimmune patterns. Nature 601, 118–124 https://doi.org/10.1038/s41586-021-04221-8 (2022).
Google Scholar
Ishikawa, H. & Barber, G. N. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 455, 674–678 https://doi.org/10.1038/nature07317 (2008).
Google Scholar
Sun, L., Wu, J., Du, F., Chen, X. & Chen, Z. J. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339, 786–791 https://doi.org/10.1126/science.1232458 (2013).
Google Scholar
Muruve, D. A. et al. The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response. Nature 452, 103–107 https://doi.org/10.1038/nature06664 (2008).
Google Scholar
Fernandes-Alnemri, T., Yu, J.-W., Datta, P., Wu, J. & Alnemri, E. S. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458, 509–513 https://doi.org/10.1038/nature07710 (2009).
Google Scholar
Hornung, V. et al. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458, 514–518 https://doi.org/10.1038/nature07725 (2009).
Google Scholar
Bürckstümmer, T. et al. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nat. Immunol. 10, 266–272 https://doi.org/10.1038/ni.1702 (2009).
Google Scholar
Roberts, T. L. et al. HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA. Science 323, 1057–1060 https://doi.org/10.1126/science.1169841 (2009).
Google Scholar
White, H. D., Roeder, D. A. & Green, W. R. An immunodominant Kb-restricted peptide from the p15E transmembrane protein of endogenous ecotropic murine leukemia virus (MuLV) AKR623 that restores susceptibility of a tumor line to anti-AKR/Gross MuLV cytotoxic T lymphocytes. J. Virol. 68, 897–904 https://doi.org/10.1128/jvi.68.2.897-904.1994 (1994).
Google Scholar
White, H. D., Roeder, D. A., Lam, T. & Green, W. R. Major and minor Kb-restricted epitopes encoded by the endogenous ecotropic murine leukemia virus AKR623 that are recognized by anti-AKR/Gross MuLV CTL. Viral Immunol. 7, 51–59 https://doi.org/10.1089/vim.1994.7.51 (1994).
Google Scholar
Sijts, A. J. et al. Identification of an H-2 Kb-presented Moloney murine leukemia virus cytotoxic T-lymphocyte epitope that displays enhanced recognition in H-2 Db mutant bm13 mice. J. Virol. 68, 6038–6046 https://doi.org/10.1128/jvi.68.9.6038-6046.1994 (1994).
Google Scholar
Lyu, Y. et al. Stem cell activity-coupled suppression of endogenous retrovirus governs adult tissue regeneration. Cell https://doi.org/10.1016/j.cell.2024.10.007 (2024).
Globig, A.-M. et al. The β1-adrenergic receptor links sympathetic nerves to T cell exhaustion. Nature 622, 383–392 https://doi.org/10.1038/s41586-023-06568-6 (2023).
Google Scholar
Kaplan, D. H., Jenison, M. C., Saeland, S., Shlomchik, W. D. & Shlomchik, M. J. Epidermal langerhans cell-deficient mice develop enhanced contact hypersensitivity. Immunity 23, 611–620 https://doi.org/10.1016/j.immuni.2005.10.008 (2005).
Google Scholar
Abraira, V. E. et al. The cellular and synaptic architecture of the mechanosensory dorsal horn. Cell 168, 295–310 https://doi.org/10.1016/j.cell.2016.12.010 (2017).
Google Scholar
Madisen, L. et al. A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat. Neurosci. 13, 133–140 https://doi.org/10.1038/nn.2467 (2010).
Google Scholar
Overwijk, W. W. et al. Tumor regression and autoimmunity after reversal of a functionally tolerant state of self-reactive CD8+ T Cells. J. Exp. Med. 198, 569–580 https://doi.org/10.1084/jem.20030590 (2003).
Google Scholar
Ji, Y. et al. Identification of the genomic insertion site of Pmel-1 TCR α and β transgenes by next-generation sequencing. PLoS ONE 9, e96650 https://doi.org/10.1371/journal.pone.0096650 (2014).
Google Scholar
Lewandoski, M., Meyers, E. N. & Martin, G. R. Analysis of Fgf8 gene function in vertebrate development. Cold Spring Harb. Symp. Quant. Biol. 62, 159–168 (1997).
Google Scholar
Dassule, H. R., Lewis, P., Bei, M., Maas, R. & McMahon, A. P. Sonic hedgehog regulates growth and morphogenesis of the tooth. Development 127, 4775–4785 https://doi.org/10.1242/dev.127.22.4775 (2000).
Google Scholar
Ge, J., Gong, Y.-N., Xu, Y. & Shao, F. Preventing bacterial DNA release and absent in melanoma 2 inflammasome activation by a Legionella effector functioning in membrane trafficking. Proc. Natl Acad. Sci. 109, 6193–6198 https://doi.org/10.1073/pnas.1117490109 (2012).
Google Scholar
Ma, C. et al. AIM2 controls microglial inflammation to prevent experimental autoimmune encephalomyelitis. J. Exp. Med. 218, e20201796 https://doi.org/10.1084/jem.20201796 (2021).
Google Scholar
Zhu, H. et al. β1-adrenoceptor in the central amygdala is required for unconditioned stimulus-induced drug memory reconsolidation. Int. J. Neuropsychopharmacol. 21, 267–280 https://doi.org/10.1093/ijnp/pyx104 (2018).
Google Scholar
Xu, Z. et al. Embryonic attenuated Wnt/β-catenin signaling defines niche location and long-term stem cell fate in hair follicle. eLife 4, e10567 https://doi.org/10.7554/eLife.10567 (2015).
Google Scholar
Riol-Blanco, L. et al. Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation. Nature 510, 157–161 https://doi.org/10.1038/nature13199 (2014).
Google Scholar
Peterson, S. C., Brownell, I. & Wong, S. Y. Cutaneous surgical denervation: a method for testing the requirement for nerves in mouse models of skin disease. J. Vis. Exp. https://doi.org/10.3791/54050 (2016).
Zhou, Y. et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun. 10, 1523 https://doi.org/10.1038/s41467-019-09234-6 (2019).
Google Scholar
