Peripheral immune-inducer dendritic cells drive early-life allergic inflammation PMID: 41741647

ADC Targets in Oncology

2026-04-10

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

Nature. 2026 Apr;652(8112):1308-1317. doi: 10.1038/s41586-026-10162-x.

Yue Xing ¹ , Ilana Reznikov ² , Abonti Nur Ahmed ² , Ikjot Sidhu ² , Jill Wisnewski ³ , Asma Farhat ² , Aleksandr Prystupa ² , Piotr Konieczny ⁴ , Kody Mansfield ⁵ , Melissa L Cooper ⁶ , Stephen T Yeung ⁷ , Madeline Kim ⁸ , Sophia Adeghe ⁹ , Katherine D Gaines ² , Meredith Manson ⁸ , Ji Hyun Sim ¹⁰ ¹¹ , Qingrong Huang ¹² , Ata S Moshiri ¹³ , Kamal M Khanna ¹⁴ ¹⁵ , Theresa T Lu ¹⁰ ¹¹ , Emma Guttman-Yassky ⁸ , Amanda W Lund ¹³ ¹⁴ ¹⁶ , Niroshana Anandasabapathy ⁹ ¹⁷ , Shruti Naik ¹⁸ ¹⁹

Affiliations

1. Department of Immunology and Immunotherapy, Precision Immunology Institute, Icahn School of Medicine at Mt Sinai, New York, NY, USA. [email protected].
2. Department of Immunology and Immunotherapy, Precision Immunology Institute, Icahn School of Medicine at Mt Sinai, New York, NY, USA.
3. Department of Biology, MIT, Cambridge, MA, USA.
4. Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.
5. Department of Cell Biology, NYU Langone Health, New York, NY, USA.
6. Neuroscience Institute, NYU Medical Center, New York, NY, USA.
7. Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
8. Kimberly and Eric J Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
9. Department of Dermatology, Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.
10. Inflammation and Autoimmunity Program, Hospital for Special Surgery Research Institute, New York, NY, USA.
11. Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.
12. Center for Discovery & Innovation, Hackensack Meridian Health, Nutley, NJ, USA.
13. Ronald O. Perelman Department of Dermatology, NYU Grossman School of Medicine, NYU Langone Health, New York, NY, USA.
14. Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, NYU Langone Health, New York, NY, USA.
15. Department of Microbiology, NYU Grossman School of Medicine, NYU Langone Health, New York, NY, USA.
16. Department of Pathology, NYU Langone Health, New York, NY, USA.
17. Englander Institute for Precision Medicine, Parker Institute for Cancer Immunotherapy, Sandra and Edward Meyer Cancer Center, Immunology and Microbial Pathogenesis Program at Weill Cornell Medicine, New York, NY, USA.
18. Department of Immunology and Immunotherapy, Precision Immunology Institute, Icahn School of Medicine at Mt Sinai, New York, NY, USA. [email protected].
19. Kimberly and Eric J Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. [email protected].

Abstract

Atopic diseases associated with allergens, as well as allergic diseases, frequently arise early in life; however, the age-dependent mechanisms governing immune responses to allergens remain poorly understood¹. Here we find that in early life, exposure to common allergens triggers a distinct bifurcated immune response, simultaneously triggering type 17 inflammation in the skin and initiating canonical T helper 2 sensitization in the lymph nodes. This early-life γδ type 17-mediated dermatitis primes the exaggerated allergic lung inflammation upon secondary allergen exposure. Mechanistically, we find dendritic cell (DC)-mediated type 17 activation directly in the skin without requiring migration to lymph nodes; we term this state 'peripheral immune inducer' (pii) DC. CD301b⁺ conventional type 2 DCs acquire allergen, adopt the pii-DC state, produce IL-23 and activate local γδ type 17 cells independently of lymph-node engagement. The pii-DC state is enabled by the immature hypothalamic-pituitary-adrenal axis and physiologically low systemic glucocorticoids characteristic of early life^2,3; DC-specific deletion of the Glucocorticoid Receptor recapitulates the pii-DC phenotype. These findings define a developmental checkpoint, set by neuroendocrine maturation, that enables in situ DC activation and immune induction, thereby shaping age-dependent responses to allergens.