Long-term tolerance to skin commensals is established neonatally through a specialized dendritic cell subgroup

Antonin Weckel; Miqdad O Dhariwala; Kevin Ly; Victoria M Tran; Oluwasunmisola T Ojewumi; Julianne B Riggs; Jeanmarie R Gonzalez; Laura R Dwyer; Joy N Okoro; John M Leech; Margot S Bacino; Grace D Cho; Geil Merana; Niroshana Anandasabapathy; Yosuke Kumamoto; Tiffany C Scharschmidt

doi:10.1016/j.immuni.2023.03.008

Long-term tolerance to skin commensals is established neonatally through a specialized dendritic cell subgroup

Immunity. 2023 Jun 13;56(6):1239-1254.e7. doi: 10.1016/j.immuni.2023.03.008. Epub 2023 Apr 6.

Authors

Antonin Weckel¹, Miqdad O Dhariwala¹, Kevin Ly², Victoria M Tran², Oluwasunmisola T Ojewumi¹, Julianne B Riggs³, Jeanmarie R Gonzalez², Laura R Dwyer², Joy N Okoro¹, John M Leech¹, Margot S Bacino⁴, Grace D Cho⁵, Geil Merana¹, Niroshana Anandasabapathy⁶, Yosuke Kumamoto⁷, Tiffany C Scharschmidt⁸

Affiliations

¹ University of California, San Francisco, Department of Dermatology, San Francisco, CA 94143, USA.
² University of California, San Francisco, Department of Dermatology, San Francisco, CA 94143, USA; University of California, San Francisco, Biomedical Sciences Graduate Program, San Francisco, CA 94143, USA.
³ University of California, San Francisco, Biomedical Sciences Graduate Program, San Francisco, CA 94143, USA.
⁴ University of California, San Francisco, Oral and Craniofacial Sciences Graduate Program, San Francisco, CA 94143, USA.
⁵ University of California, San Francisco, Department of Dermatology, San Francisco, CA 94143, USA; University of California, Los Angeles, Department of Infectious Diseases, Los Angeles, CA 90095, USA.
⁶ Department of Dermatology, Meyer Cancer Center, Englander Institute for Precision Medicine, Weill Cornell Medical College, New York, NY, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Medical College, New York, NY, USA.
⁷ Department of Pathology, Immunology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA; Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.
⁸ University of California, San Francisco, Department of Dermatology, San Francisco, CA 94143, USA. Electronic address: tiffany.scharschmidt@ucsf.edu.

PMID: 37028427
PMCID: PMC10330031 (available on 2024-06-13)
DOI: 10.1016/j.immuni.2023.03.008

Abstract

Early-life establishment of tolerance to commensal bacteria at barrier surfaces carries enduring implications for immune health but remains poorly understood. Here, we showed that tolerance in skin was controlled by microbial interaction with a specialized subset of antigen-presenting cells. More particularly, CD301b⁺ type 2 conventional dendritic cells (DCs) in neonatal skin were specifically capable of uptake and presentation of commensal antigens for the generation of regulatory T (Treg) cells. CD301b⁺ DC2 were enriched for phagocytosis and maturation programs, while also expressing tolerogenic markers. In both human and murine skin, these signatures were reinforced by microbial uptake. In contrast to their adult counterparts or other early-life DC subsets, neonatal CD301b⁺ DC2 highly expressed the retinoic-acid-producing enzyme, RALDH2, the deletion of which limited commensal-specific Treg cell generation. Thus, synergistic interactions between bacteria and a specialized DC subset critically support early-life tolerance at the cutaneous interface.

Keywords: Staphylococcus epidermidis; commensal bacteria; commensals; dendritic cells; early-life immunity; neonatal immunity; regulatory T cells; retinoic acid; skin; tolerance.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aldehyde Oxidoreductases / metabolism
Animals
Dendritic Cells*
Humans
Immune Tolerance
Mice
Skin*
T-Lymphocytes, Regulatory

Substances

RALDH2 protein, mouse
Aldehyde Oxidoreductases

Abstract

Publication types

MeSH terms

Substances

Grants and funding