Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote TH2 and inhibit TH17 cell polarization

Mayer, Johannes U; Hilligan, Kerry L.; Chandler, Jodie; Eccles, David; Old, Samuel I; Domingues, Rita G.; Yang, Jianping; Webb, Greta R; Munoz‐Erazo, Luis; Hyde, Evelyn; Wakelin, Kirsty A.; Tang, Shiau-Choot; Chappell, Sally Claire; Daake, Sventja von; Brombacher, Frank; Mackay, Charles R.; Sher, Alan; Tussiwand, Roxane; Connor, Lisa M.; Gallego‐Ortega, David; Janković, Dragana; Gros, Graham Le; Hepworth, Matthew R.; Lamiable, Olivier; Ronchese, Franca

doi:10.1038/s41590-021-01067-0

Cited by 84 publications

(100 citation statements)

References 72 publications

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“…While cDC1s depend on the transcription factor IRF8 for their development and are specialized into cross-presenting cell-associated antigens to CD8 + T cells, cDC2s are IRF8 independent and more preferentially are required for CD4 + T-cell priming and Th responses. 2,3 Mayer et al 1 examined the cDC populations in the mouse skin and found that cDC2s can be separated into CD11b hi and CD11b lo fractions, a finding compatible with previous studies. 4,5 CD11b lo cDC2s were absent from other tissues examined, including the small intestine and lung, suggestive of the existence of a particular milieu imprinting cDC2 diversity in the skin.…”

supporting

confidence: 79%

“…Although this observation corroborated a previous finding, 4 it is difficult to reconcile with the key role proposed for dermal cDC2s expressing CD301b/ MGL2 in mediating Th2 immunity, 7 as a later study showed that CD301b expression is restricted to the same skin migratory CD11b hi cDC2s 4 that Mayer et al demonstrated are IL-13 independent. 1 The nature of this discrepancy warrants further investigation.…”

mentioning

confidence: 96%

“…To search for the cellular source of IL-13 in the skin, Mayer et al 1 used an IL-13-DsRed reporter strain and found that approximately half of the constitutive IL-13 expressing cells were type 2 innate lymphoid cells (ILC2s). This agrees with a previous report identifying ILCs as the main source of IL-13 in unchallenged murine skin.…”

mentioning

confidence: 99%

“…Mayer et al 1 then investigated whether this signaling axis also plays a role in the immune response in the skin. To exclude roles for this pathway in non-cDCs, such as T cells, these studies were conducted in chimeric mice where all cDC2s where either wild type or STAT6 deficient and the wild-type T cells could be identified based on congenic markers.…”

mentioning

confidence: 99%

“…Collectively, the study by Mayer et al 1 adds to a growing body of evidence of tissue cDC2 diversity, identifying a unique subset of cDC2s in the skin that impacts on the capacity of the immune system to promote Th2 immunity. Although the IL-13-STAT6 homeostatic axis may be restricted to the skin, cDC2 diversity is apparent in other tissues, as, for example, has been shown in the lung after allergen challenge.…”

mentioning

confidence: 99%

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ILC2‐derived IL‐13 promotes skin cDC2 diversity

Nutt

Chopin

2021

Immunol Cell Biol

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supporting

confidence: 79%

mentioning

confidence: 96%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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ILC2‐derived IL‐13 promotes skin cDC2 diversity

Nutt

Chopin

2021

Immunol Cell Biol

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Langerhans cells in the skin and oral mucosa: Brothers in arms?

2023

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The skin and the oral mucosa represent interfaces to the environment that are constantly exposed to pathogens and harmless foreign antigens such as commensal bacteria. Both barrier organs share the presence of Langerhans cells (LC), distinctive members of the heterogeneous family of antigen‐presenting dendritic cells (DC) that have the unique ability to promote tolerogenic as well as inflammatory immune responses. While skin LC have been extensively studied in the past decades, less is known about the function of oral mucosal LC. Despite similar transcriptomic signatures, skin and oral mucosal LC differ greatly in their ontogeny and development. In this review article, we will summarize the current knowledge on LC subsets in the skin compared to the oral mucosa. We will discuss the similarities and differences in their development, homeostasis, and function in the two barrier tissues, including their interaction with the local microbiota. In addition, this review will update recent advances on the role of LC in inflammatory skin and oral mucosal diseases.

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Classical DC2 subsets and monocyte‐derived DC: Delineating the developmental and functional relationship

2023

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To specifically tailor immune responses to a given pathogenic threat, dendritic cells (DC) are highly heterogeneous and comprise many specialized subtypes, including conventional DC (cDC) and monocyte‐derived DC (MoDC), each with distinct developmental and functional characteristics. However, the functional relationship between cDC and MoDC is not fully understood, as the overlapping phenotypes of certain type 2 cDC (cDC2) subsets and MoDC do not allow satisfactory distinction of these cells in the tissue, particularly during inflammation. However, precise cDC2 and MoDC classification is required for studies addressing how these diverse cell types control immune responses and is therefore currently one of the major interests in the field of cDC research. This review will revise murine cDC2 and MoDC biology in the steady state and under inflammatory conditions and discusses the commonalities and differences between ESAMlo cDC2, inflammatory cDC2, and MoDC and their relative contribution to the initiation, propagation, and regulation of immune responses.

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Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote TH2 and inhibit TH17 cell polarization

Cited by 84 publications

References 72 publications

ILC2‐derived IL‐13 promotes skin cDC2 diversity

ILC2‐derived IL‐13 promotes skin cDC2 diversity

Langerhans cells in the skin and oral mucosa: Brothers in arms?

Classical DC2 subsets and monocyte‐derived DC: Delineating the developmental and functional relationship

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