IL-17A–Producing Innate Lymphoid Cells Promote Skin Inflammation by Inducing IL-33–Driven Type 2 Immune Responses

Kim, Min Ho; Jin, Seon Pil; Jang, Sunhyae; Choi, Ji Yeob; Chung, Doo Hyun; Lee, Dong Hun; Kim, Kyu Han; Kim, Hye Young

doi:10.1016/j.jid.2019.08.447

Cited by 23 publications

(23 citation statements)

References 38 publications

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“…This and our results suggest the connection between ILC2/3 and PA for the development of AD. It has been shown that increased ILC2s and ILC3s worsened atopic dermatitis 98 . However, we don’t have data that indicate increased PA act directly on ILCs.…”

Section: Discussionmentioning

confidence: 99%

Long-chain saturated fatty acids in breast milk are associated with the pathogenesis of atopic dermatitis via induction of inflammatory ILC3s

Kong

Tsuyama

Inoue

et al. 2021

Sci Rep

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Breastfeeding influences the immune system development in infants and may even affect various immunological responses later in life. Breast milk provides a rich source of early nutrition for infant growth and development. However, the presence of certain compounds in breast milk, related to an unhealthy lifestyle or the diet of lactating mothers, may negatively impact infants. Based on a cohort study of atopic dermatitis (AD), we find the presence of damage-associated molecular patterns (DAMPs) activity in the mother’s milk. By non-targeted metabolomic analysis, we identify the long-chain saturated fatty acids (LCSFA) as a biomarker DAMPs (+) breast milk samples. Similarly, a mouse model in which breastfed offspring are fed milk high in LCSFA show AD onset later in life. We prove that LCSFA are a type of damage-associated molecular patterns, which initiate a series of inflammatory events in the gut involving type 3 innate lymphoid cells (ILC3s). A remarkable increase in inflammatory ILC3s is observed in the gut, and the migration of these ILC3s to the skin may be potential triggers of AD. Gene expression analysis of ILC3s isolated from the gut reveal upregulation of genes that increase ILC3s and chemokines/chemokine receptors, which may play a role in ILC migration to the skin. Even in the absence of adaptive immunity, Rag1 knockout mice fed a high-LCSFA milk diet develop eczema, accompanied by increased gut ILC3s. We also present that gut microbiota of AD-prone PA milk-fed mice is different from non-AD OA/ND milk-fed mice. Here, we propose that early exposure to LCSFAs in infants may affect the balance of intestinal innate immunity, inducing a highly inflammatory environment with the proliferation of ILC3s and production of interleukin-17 and interleukin-22, these factors may be potential triggers or worsening factors of AD.

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Section: Discussionmentioning

confidence: 99%

Long-chain saturated fatty acids in breast milk are associated with the pathogenesis of atopic dermatitis via induction of inflammatory ILC3s

Kong

Tsuyama

Inoue

et al. 2021

Sci Rep

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“…Thus, IL-17 may be an important mediator of TWEAK-induced AD-like inflammation. The numbers of ILC3, expressing IL-17, in the skin of AD-induced mice were increased, and that neutralizing IL-17A delayed development of AD in the mouse model [45]. ILC3 induced IL-33 production by keratinocytes and fibroblasts.…”

Section: Ad Mouse Models and Th17-related Cytokinesmentioning

confidence: 94%

The Role of Th17-Related Cytokines in Atopic Dermatitis

Sugaya

2020

IJMS

150

102

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T helper-17 (Th17) cells, which mainly produce IL-17, are associated with development of various autoimmune diseases such as rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and psoriasis. IL-17 and related cytokines are therapeutic targets of these diseases. In atopic dermatitis (AD), Th2 cytokines such as IL-4 and IL-13 are regarded to be the main player of the disease; however, Th17 cytokines are also expressed in AD skin lesions. Expression of IL-22 rather than IL-17 is predominant in AD skin, which is contrary to cytokine expression in psoriasis skin. Relatively low IL-17 expression in AD skin can induce relatively low antimicrobial peptide expression, which may be a reason why bacterial infection is frequently seen in AD patients. Failure of clinical trials for investigating the efficacy of anti-IL-12/23 p40 in AD has suggested that IL-17 expressed in skin lesions should not be the main player but a bystander responding to barrier dysfunction.

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“…Atopic dermatitis (AD) is a common inflammatory skin disorder characterized by high levels of IL-4, IL-5 and IL-13 ( 151 , 152 ). AD skin lesions are enriched for skin-resident ILC2s, which are activated by TSLP or IL-33, promoting type 2 inflammation ( 132 , 153 , 154 ). This is supported by murine models where anti-CD90 and anti-CD25 depletion of skin ILC2s in T and B cell deficient Rag1 -/- mice attenuated dermatitis symptoms ( 153 ).…”

Section: Ilcs In the Skinmentioning

confidence: 99%

Tissue-Dependent Adaptations and Functions of Innate Lymphoid Cells

et al. 2022

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Tissue-resident immune cells reside in distinct niches across organs, where they contribute to tissue homeostasis and rapidly respond to perturbations in the local microenvironment. Innate lymphoid cells (ILCs) are a family of innate immune cells that regulate immune and tissue homeostasis. Across anatomical locations throughout the body, ILCs adopt tissue-specific fates, differing from circulating ILC populations. Adaptations of ILCs to microenvironmental changes have been documented in several inflammatory contexts, including obesity, asthma, and inflammatory bowel disease. While our understanding of ILC functions within tissues have predominantly been based on mouse studies, development of advanced single cell platforms to study tissue-resident ILCs in humans and emerging patient-based data is providing new insights into this lymphocyte family. Within this review, we discuss current concepts of ILC fate and function, exploring tissue-specific functions of ILCs and their contribution to health and disease across organ systems.

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IL-17A–Producing Innate Lymphoid Cells Promote Skin Inflammation by Inducing IL-33–Driven Type 2 Immune Responses

Cited by 23 publications

References 38 publications

Long-chain saturated fatty acids in breast milk are associated with the pathogenesis of atopic dermatitis via induction of inflammatory ILC3s

Long-chain saturated fatty acids in breast milk are associated with the pathogenesis of atopic dermatitis via induction of inflammatory ILC3s

The Role of Th17-Related Cytokines in Atopic Dermatitis

Tissue-Dependent Adaptations and Functions of Innate Lymphoid Cells

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