Innate type 2 immunity controls hair follicle commensalism by Demodex mites

Ricardo-González, Roberto R.; Kotas, Maya E.; O’Leary, Claire E.; Singh, Katelyn; Damsky, William; Liao, Chang; Arouge, Elizabeth; Tenvooren, Iliana; Márquez, Diana M.; Schroeder, Andrew; Cohen, Jarish N.; Fassett, Marlys S.; Lee, Jun Young; Daniel, Scott G.; Bittinger, Kyle; Díaz, Roberto; Fraser, James S.; Ali, Nasreen; Ansel, K. Mark; Spitzer, Matthew H.; Liang, Hong-Erh; Locksley, Richard M.

doi:10.1016/j.immuni.2022.08.001

Cited by 14 publications

(9 citation statements)

References 80 publications

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“…In line, AD skin has been demonstrated to harbor Mala s13-reactive T-cells that can contribute to skin inflammation 100 . In addition, recent experiments in Demodex infected IL4ra -/- mice have demonstrated that the absence of type 2 immunity can lead to Demodex outgrowth and aberrant cutaneous inflammation 101 . Consistently, patients with severe Demodex -associated skin diseases such as rhinophyma show increased expression levels of IL-22 and IFN-γ along with decreased IL-13 levels within the skin 101 .…”

Section: Discussionmentioning

confidence: 99%

Dupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells

Bangert,

Alkon,

Chennareddy

et al. 2024

Nat Commun

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Dupilumab, an IL4R-blocking antibody, has shown clinical efficacy for atopic dermatitis (AD) treatment. In addition to conjunctivitis/blepharitis, the de novo appearance of head/neck dermatitis is now recognized as a distinct side effect, occurring in up to 10% of patients. Histopathological features distinct from AD suggest a drug effect, but exact underlying mechanisms remain unknown. We profiled punch biopsies from dupilumab-associated head and neck dermatitis (DAHND) by using single-cell RNA sequencing and compared data with untreated AD and healthy control skin. We show that dupilumab treatment was accompanied by normalization of IL-4/IL-13 downstream activity markers such as CCL13, CCL17, CCL18 and CCL26. By contrast, we found strong increases in type 22-associated markers (IL22, AHR) especially in oligoclonally expanded T cells, accompanied by enhanced keratinocyte activation and IL-22 receptor upregulation. Taken together, we demonstrate that dupilumab effectively dampens conventional type 2 inflammation in DAHND lesions, with concomitant hyperactivation of IL22-associated responses.

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Section: Discussionmentioning

confidence: 99%

Dupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells

Bangert,

Alkon,

Chennareddy

et al. 2024

Nat Commun

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“…Demodex spp. feed on sebum and keratinocyte debris [ 20 ], and although they are not the direct cause of AGA, prolonged infestation by the parasite causes the hair cycle from anagen to telogen and follicle depletion [ 21 ]. Although many aspects of dissecting folliculitis of the scalp, associated with patchy hair loss [ 22 ], are yet to be elucidated, an inflammatory reaction is suggested due to the presence of microorganisms such as Demodex spp.…”

Section: Demodicosis Etiology and Coinfectionsmentioning

confidence: 99%

“…It is indicated that in patients with rosacea, there is an increase in folliculitis associated with the presence of Demodex spp., which correlates with a decrease in type 2 cytokines (IL-2). Research by Ricardo-Gonzalez et al, 2022 [ 20 ] in animal models showed the key role of the so-called immune checkpoint, which includes, coupled with the hair growth cycle dermal ILC2 (innate lymphoid cells) and IL-13, maintaining skin integrity and reducing pathological Demodex spp. mite infestation.…”

Section: Demodicosis Etiology and Coinfectionsmentioning

confidence: 99%

“…It was observed that as a result of their dysfunction and the loss of such a barrier, colonization of Demodex spp. resulted in increased epithelial proliferation and, through the current inflammation, genetic changes in repair programs, which consequently led to the depletion of the hair follicles [ 20 ]. Moreover, Demodex spp.…”

Section: Demodicosis Etiology and Coinfectionsmentioning

confidence: 99%

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Demodicosis in Different Age Groups and Alternative Treatment Options—A Review

Chudzicka-Strugała

Gołębiewska

Brudecki³

et al. 2023

JCM

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Infestation with Demodex mites is a common occurrence, especially in adults and the elderly. More recent attention has been paid to the presence of Demodex spp. mites in children, even ones without comorbidities. It causes both dermatological and ophthalmological problems. The presence of Demodex spp. is often asymptomatic, thus it is suggested to include parasitological investigation tests in dermatological diagnostics, in addition to bacteriological analysis. Literature reports show that Demodex spp. are related to the pathogenesis of numerous dermatoses, including rosacea or demodicosis gravis, and common eye pathologies reported by patients such as dry eye syndrome or ocular surface inflammatory conditions, such as blepharitis, chalazia, Meibomian gland dysfunction, and keratitis. Treatment of patients is a challenge and is usually prolonged, therefore it is important to carefully diagnose and properly select the therapy regimen for the treatment to be successful, and with minimal side effects, especially for young patients. Apart from the use of essential oils, research is ongoing for new alternative preparations active against Demodex sp. Our review was focused on the analysis of the current literature data on the available agents in the treatment of demodicosis in adults and children.

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“…Demodex is controlled by its host through innate type 2 immunity (Ricardo-gonzalez et al, 2022). This raises the question whether primary demodicosis in humans exists at all.…”

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confidence: 99%

Our life companions: the human follicular mite Demodex folliculorum

Perotti

Braig

2022

Zoosymposia

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We carry them in our skin pores through our entire life, from birth to death. We offer them shelter and in return, they tidy-up our pores. We go on with our busy day life and they sleep. They wake up when we go to sleep and while we are deeply dreaming, they move around, visit other pores and mates, and reproduce. Despite being our ‘very own’ life companions, until recently, we knew very little about their struggle.

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Innate type 2 immunity controls hair follicle commensalism by Demodex mites

Cited by 14 publications

References 80 publications

Dupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells

Dupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells

Demodicosis in Different Age Groups and Alternative Treatment Options—A Review

Our life companions: the human follicular mite Demodex folliculorum

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