Early-life inflammation primes a T helper 2 cell–fibroblast niche in skin

Boothby, Ian C.; Kinet, Maxime J; Boda, Devi P; Kwan, Elaine; Clancy, Sean; Cohen, Jarish N.; Habrylo, Ireneusz; Lowe, Margaret M.; Pauli, Mariela; Yates, Ashley E.; Chan, Jamie D.; Harris, Hobart W.; Neuhaus, Isaac M.; McCalmont, Timothy H.; Molofsky, Ari B.; Rosenblum, Michael D.

doi:10.1038/s41586-021-04044-7

Cited by 46 publications

(44 citation statements)

References 36 publications

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“…Injection of an agent that inflames the pancreas led to transcriptional and epigenetic changes in pancreatic acinar cells that reduced their inflammatory response to a subsequent challenge, while promoting their malignant transformation ( Del Poggetto et al., 2021 ). Transient induction of inflammation in neonatal mice led to accumulation of Th2 cells alongside dermal fibroblasts, which led in turn to changes in fibroblastic responses to a subsequent injury ( Boothby et al., 2021 ).…”

Section: Inflammatory Memorymentioning

confidence: 99%

Nonresolving inflammation redux

Nathan

2022

Immunity

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Section: Inflammatory Memorymentioning

confidence: 99%

Nonresolving inflammation redux

Nathan

2022

Immunity

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“…Th2 cells subsequently traffic back to the skin where they reside as Th2-Trm and drive hallmark features of atopic dermatitis—inflammatory cell recruitment and epidermal hyperplasia. Recent studies also suggest that timing may be important for skin sensitization, as early life skin inflammation in mice enables a Th2-Trm niche with stromal cells in the skin ( 34 ). In the model of food allergy, systemic IL-33 produced by damaged keratinocytes synergizes with IL-25 produced by intestinal tuft cells ( 35 ) to promote activation and expansion of ILC2s in the gut, which in turn produce IL-4 locally to activate and expand mast cells to cause anaphylaxis following oral rechallenge with allergen ( 30 ) ( Figures 1B–D ).…”

Section: Disorders Of Barrier Functionmentioning

confidence: 99%

Inborn Errors of the Immune System Associated With Atopy

2022

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Atopic disorders, including atopic dermatitis, food and environmental allergies, and asthma, are increasingly prevalent diseases. Atopic disorders are often associated with eosinophilia, driven by T helper type 2 (Th2) immune responses, and triggered by disrupted barrier function leading to abnormal immune priming in a susceptible host. Immune deficiencies, in contrast, occur with a significantly lower incidence, but are associated with greater morbidity and mortality. A subset of atopic disorders with eosinophilia and elevated IgE are associated with monogenic inborn errors of immunity (IEI). In this review, we discuss current knowledge of IEI that are associated with atopy and the lessons these immunologic disorders provide regarding the fundamental mechanisms that regulate type 2 immunity in humans. We also discuss further mechanistic insights provided by animal models.

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“…Distinctive clinical features and incidences of type 2 inflammatory dermatosis between the young and the elderly are observed, and the difference is often thought to be caused by aging-related changes including immunosenescence, but direct evidence remains insufficient. As evidenced by the recent discovery of TH2-interacting fascial fibroblasts (TIFFs) in mouse and human skin, skin-resident or -infiltrating immune cells and stromal cells are complexly interacting and influence each other throughout life ( Boothby, et al, 2021 ). They undergo structural and functional alterations simultaneously, but overall, inflammaging phenotype characterizes the skin microenvironment during normal aging.…”

Section: Future Needsmentioning

confidence: 99%

Skin Immunosenescence and Type 2 Inflammation: A Mini-Review With an Inflammaging Perspective

Chen

Yang

Song

et al. 2022

Front. Cell Dev. Biol.

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Skin-resident stromal cells, including keratinocytes, fibroblasts, adipocytes, and immune cells including Langerhans cells, dendritic cells, T cells, and innate lymphoid cells, and their functional products work in concert to ensure the realization of skin barrier immunity. However, aging-induced immunosenescence predisposes the elderly to pruritic dermatoses, including type 2 inflammation-mediated. Inflammaging, characterized by chronic low level of pro-inflammatory cytokines released from senescent cells with the senescence-associated secretory phenotype (SASP), may drive immunosenescence and tangle with type 2 inflammatory dermatoses. The present mini-review summarizes current evidence on immunosenescence and type 2 inflammation in the skin and further focuses on future needs from an inflammaging perspective to clarify their complexity.

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Early-life inflammation primes a T helper 2 cell–fibroblast niche in skin

Cited by 46 publications

References 36 publications

Nonresolving inflammation redux

Nonresolving inflammation redux

Inborn Errors of the Immune System Associated With Atopy

Skin Immunosenescence and Type 2 Inflammation: A Mini-Review With an Inflammaging Perspective

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