Peripheral immune-inducer dendritic cells drive early-life allergic inflammation

Nature News · Feb 25, 2026 · Collected from RSS

Full Article

Data availabilityAll data to support the conclusions in this article can be found in the main text, extended data, supplementary information and source data. All genomic data generated in this study are publicly available at the Gene Expression Omnibus under accession numbers GSE273131, GSE299934 and GSE273161. The M. musculus reference genome (mm10/GRCm38) was used for sequencing alignment. We reanalysed the following publicly available dataset: GSE180542, GSE30999, public-accessible supplementary tables from Ewald et al.11, Dhingra et al.13, Renert-Yuval et al.19 and Del Duca et al.20. Source data are provided with this paper.ReferencesPierau, M., Arra, A. & Brunner-Weinzierl, M. C. Preventing atopic diseases during childhood — early exposure matters. Front. Immunol. 12, 617731 (2021).Article PubMed PubMed Central CAS Google Scholar Bakker, J. M., van Bel, F. & Heijnen, C. J. Neonatal glucocorticoids and the developing brain: short-term treatment with life-long consequences? Trends Neurosci. 24, 649–653 (2001).Article PubMed CAS Google Scholar Kaplan, H. S. et al. Sensory input, sex and function shape hypothalamic cell type development. Nature 647, 157–168 (2025).Article ADS PubMed PubMed Central CAS Google Scholar Smith, N. L. et al. Developmental origin governs CD8+ T cell fate decisions during infection. Cell 174, 117–130.e14 (2018).Article PubMed CAS Google Scholar Biagini Myers, J. M. & Khurana Hershey, G. K. Eczema in early life: genetics, the skin barrier, and lessons learned from birth cohort studies. J. Pediatr. 157, 704–714 (2010).Article PubMed PubMed Central Google Scholar Schoos, A. M. Atopic diseases — diagnostics, mechanisms, and exposures. Pediatr. Allergy Immunol. 35, e14198 (2024).Article PubMed CAS Google Scholar Sakamoto, K. & Nagao, K. Mouse models for atopic dermatitis. Curr. Protoc. 3, e709 (2023).Article PubMed PubMed Central CAS Google Scholar Celedon, J. C. et al. Exposure to dust mite allergen and endotoxin in early life and asthma and atopy in childhood. J. Allergy Clin. Immunol. 120, 144–149 (2007).Article PubMed PubMed Central CAS Google Scholar Scalabrin, D. M. et al. Use of specific IgE in assessing the relevance of fungal and dust mite allergens to atopic dermatitis: a comparison with asthmatic and nonasthmatic control subjects.J. Allergy Clin. Immunol. 104, 1273–1279 (1999).Article PubMed CAS Google Scholar Salo, P. M. et al. Exposure to Alternaria alternata in US homes is associated with asthma symptoms. J. Allergy Clin. Immunol. 118, 892–898 (2006).Article PubMed PubMed Central Google Scholar Ewald, D. A. et al. Meta-analysis derived atopic dermatitis (MADAD) transcriptome defines a robust AD signature highlighting the involvement of atherosclerosis and lipid metabolism pathways. BMC Med. Genomics 8, 60 (2015).Article PubMed PubMed Central Google Scholar Suarez-Farinas, M. et al. Expanding the psoriasis disease profile: interrogation of the skin and serum of patients with moderate-to-severe psoriasis. J. Invest. Dermatol. 132, 2552–2564 (2012).Article PubMed PubMed Central CAS Google Scholar Dhingra, N. et al. Molecular profiling of contact dermatitis skin identifies allergen-dependent differences in immune response. J. Allergy Clin. Immunol. 134, 362–372 (2014).Article PubMed CAS Google Scholar Brunner, P. M. et al. Early-onset pediatric atopic dermatitis is characterized by TH2/TH17/TH22-centered inflammation and lipid alterations. J. Allergy Clin. Immunol. 141, 2094–2106 (2018).Article PubMed CAS Google Scholar Esaki, H. et al. Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin. J. Allergy Clin. Immunol. 138, 1639–1651 (2016).Article PubMed CAS Google Scholar Stamatas, G. N. et al. Early skin inflammatory biomarker is predictive of development and persistence of atopic dermatitis in infants. J. Allergy Clin. Immunol. 153, 1597–1603.e4 (2024).Article PubMed CAS Google Scholar Perner, C. et al. Substance P release by sensory neurons triggers dendritic cell migration and initiates the type-2 immune response to allergens. Immunity 53, 1063–1077.e7 (2020).Article PubMed PubMed Central CAS Google Scholar Serhan, N. et al. House dust mites activate nociceptor-mast cell clusters to drive type 2 skin inflammation. Nat. Immunol. 20, 1435–1443 (2019).Article PubMed PubMed Central CAS Google Scholar Renert-Yuval, Y. et al. The molecular features of normal and atopic dermatitis skin in infants, children, adolescents, and adults. J. Allergy Clin. Immunol. 148, 148–163 (2021).Article PubMed PubMed Central CAS Google Scholar Del Duca, E. et al. Intrapatient comparison of atopic dermatitis skin transcriptome shows differences between tape-strips and biopsies. Allergy 79, 80–92 (2024).Article PubMed Google Scholar Nakajima, S. et al. IL-17A as an inducer for Th2 immune responses in murine atopic dermatitis models. J. Invest. Dermatol. 134, 2122–2130 (2014).Article PubMed CAS Google Scholar Ajendra, J. et al. IL-17A both initiates, via IFNγ suppression, and limits the pulmonary type-2 immune response to nematode infection. Mucosal Immunol. 13, 958–968 (2020).Article PubMed PubMed Central CAS 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 (2007).Article PubMed CAS Google Scholar Kashem, S. W., Haniffa, M. & Kaplan, D. H. Antigen-presenting cells in the skin. Annu. Rev. Immunol. 35, 469–499 (2017).Article PubMed CAS Google Scholar Baeyens, A., Fang, V., Chen, C. & Schwab, S. R. Exit strategies: S1P signaling and T cell migration. Trends Immunol. 36, 778–787 (2015).Article PubMed PubMed Central CAS Google Scholar Major, J. et al. Type I and III interferons disrupt lung epithelial repair during recovery from viral infection. Science 369, 712–717 (2020).Article ADS PubMed PubMed Central CAS Google Scholar Kumamoto, Y. et al. CD301b+ dermal dendritic cells drive T helper 2 cell-mediated immunity. Immunity 39, 733–743 (2013).Article PubMed PubMed Central CAS Google Scholar Bosteels, C. et al. Inflammatory type 2 cDCs acquire features of cDC1s and macrophages to orchestrate immunity to respiratory virus infection. Immunity 52, 1039–1056.e9 (2020).Article PubMed PubMed Central CAS Google Scholar de Winde, C. M., Munday, C. & Acton, S. E. Molecular mechanisms of dendritic cell migration in immunity and cancer. Med. Microbiol. Immunol. 209, 515–529 (2020).Article PubMed PubMed Central Google Scholar Liu, J., Zhang, X., Cheng, Y. & Cao, X. Dendritic cell migration in inflammation and immunity. Cell. Mol. Immunol. 18, 2461–2471 (2021).Article PubMed PubMed Central CAS Google Scholar Hirose, K. et al. Evidence for hormonal control of heart regenerative capacity during endothermy acquisition. Science 364, 184–188 (2019).Article ADS PubMed PubMed Central CAS Google Scholar Hong, J. Y. et al. Long-term programming of CD8 T cell immunity by perinatal exposure to glucocorticoids. Cell 180, 847–861.e15 (2020).Article PubMed PubMed Central CAS Google Scholar Schmidt, M. V. et al. The postnatal development of the hypothalamic-pituitary-adrenal axis in the mouse. Int. J. Dev. Neurosci. 21, 125–132 (2003).Article PubMed CAS Google Scholar Morante-Palacios, O. et al. Coordinated glucocorticoid receptor and MAFB action induces tolerogenesis and epigenome remodeling in dendritic cells. Nucleic Acids Res. 50, 108–126 (2022).Article PubMed PubMed Central CAS Google Scholar Pieren, D. K. J., Boer, M. C. & de Wit, J. The adaptive immune system in early life: the shift makes it count. Front. Immunol. 13, 1031924 (2022).Article PubMed PubMed Central CAS Google Scholar Bee, G. C. W. et al. Age-dependent differences in efferocytosis determine the outcome of opsonophagocytic protection from invasive pathogens. Immunity 56, 1255–1268.e5 (2023).Article PubMed PubMed Central CAS Google Scholar Watson, N. B. et al. The gene regulatory basis of bystander activation in CD8+ T cells. Sci. Immunol. 9, eadf8776 (2024).Article PubMed PubMed Central CAS Google Scholar Eisenbarth, S. C. Dendritic cell subsets in T cell programming: location dictates function. Nat. Rev. Immunol. 19, 89–103 (2019).Article PubMed PubMed Central CAS Google Scholar Vantourout, P. & Hayday, A. Six-of-the-best: unique contributions of γδ T cells to immunology. Nat. Rev. Immunol. 13, 88–100 (2013).Article PubMed PubMed Central CAS Google Scholar Constantinides, M. G. et al. MAIT cells are imprinted by the microbiota in early life and promote tissue repair. Science https://doi.org/10.1126/science.aax6624 (2019).Schneider, C. et al. Tissue-resident group 2 innate lymphoid cells differentiate by layered ontogeny and in situ perinatal priming. Immunity 50, 1425–1438.e5 (2019).Article PubMed PubMed Central CAS Google Scholar Coles, M. C. et al. Role of T and NK cells and IL7/IL7r interactions during neonatal maturation of lymph nodes. Proc. Natl Acad. Sci. USA 103, 13457–13462 (2006).Article ADS PubMed PubMed Central CAS Google Scholar Wamboldt, M. Z., Laudenslager, M., Wamboldt, F. S., Kelsay, K. & Hewitt, J. Adolescents with atopic disorders have an attenuated cortisol response to laboratory stress. J. Allergy Clin. Immunol. 111, 509–514 (2003).Article PubMed CAS Google Scholar Klein, J. et al. Distinguishing features of long COVID identified through immune profiling. Nature 623, 139–148 (2023).Article ADS PubMed PubMed Central CAS Google Scholar Serhan, N. et al. Maternal stress triggers early-life eczema through fetal mast cell programming. Nature 646, 161–170 (2025).Article ADS PubMed PubMed Central CAS Google Scholar Makinen, T. et al. Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3. Nat. Med. 7, 199–205 (2001).Article PubMed CAS Google Scholar Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).Article PubMed CAS Google Scholar Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and d