Complete human CD1a deficiency on Langerhans cells due to a rare point mutation in the coding sequence

Cerny, Daniela; Le, Duyen Huynh Thi; Zuest, Roland; Kg, Srinivasan; Velumani, Sumathy; Khor, Chiea‐Chuen; Mori, Lucia; Simmons, Cameron P.; Zolezzi, Francesca; Ginhoux, Florent; Haniffa, Muzlifah; Wills, Bridget; Fink, Katja

doi:10.1016/j.jaci.2016.05.028

Cited by 4 publications

(3 citation statements)

References 19 publications

(17 reference statements)

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“…Human CD1a-deficiency has been identified and linked to increased susceptibility to tuberculosis [71][72][73] . However, abnormalities in skin barrier function and other infections have not been reported, pointing to the therapeutic targeting of CD1a.…”

Section: Discussionmentioning

confidence: 99%

CD1a promotes systemic manifestations of skin inflammation

et al. 2022

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Inflammatory skin conditions are increasingly recognised as being associated with systemic inflammation. The mechanisms connecting the cutaneous and systemic disease are not well understood. CD1a is a virtually monomorphic major histocompatibility complex (MHC) class I-like molecule, highly expressed by skin and mucosal Langerhans cells, and presents lipid antigens to T-cells. Here we show an important role for CD1a in linking cutaneous and systemic inflammation in two experimental disease models. In human CD1a transgenic mice, the toll-like receptor (TLR)7 agonist imiquimod induces more pronounced splenomegaly, expansion of the peripheral blood and spleen T cell compartments, and enhanced neutrophil and eosinophil responses compared to the wild-type, accompanied by elevated skin and plasma cytokine levels, including IL-23, IL-1α, IL-1β, MCP-1 and IL-17A. Similar systemic escalation is shown in MC903-induced skin inflammation. The exacerbated inflammation could be counter-acted by CD1a-blocking antibodies, developed and screened in our laboratories. The beneficial effect is epitope dependent, and we further characterise the five best-performing antibodies for their capacity to modulate CD1a-expressing cells and ameliorate CD1a-dependent systemic inflammatory responses. In summary, we show that a therapeutically targetable CD1a-dependent pathway may play a role in the systemic spread of cutaneous inflammation.

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Section: Discussionmentioning

confidence: 99%

CD1a promotes systemic manifestations of skin inflammation

et al. 2022

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“…Similarly, presentation of self-lipid antigen by CD1a increased IL-17 expression by CD4 + T cells in the imiquimod mouse model of psoriasis-like inflammation and in T cells isolated from psoriasis patients (194). Interestingly, CD1a deficiency in human LCs was reported but did not result in any obvious immune defect in the affected individuals (195).…”

Section: Recall and Memory T Cell Responsementioning

confidence: 93%

Antigen-Presenting Cells in the Skin

Kashem

Haniffa

Kaplan

2017

Annu. Rev. Immunol.

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274

235

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Professional antigen-presenting cells (APCs) in the skin include dendritic cells, monocytes, and macrophages. They are highly dynamic, with the capacity to enter skin from the peripheral circulation, patrol within tissue, and migrate through lymphatics to draining lymph nodes. Skin APCs are endowed with antigen-sensing, -processing, and -presenting machinery and play key roles in initiating, modulating, and resolving cutaneous inflammation. Skin APCs are a highly heterogeneous population with functionally specialized subsets that are developmentally imprinted and modulated by local tissue microenvironmental and inflammatory cues. This review explores recent advances that have allowed for a more accurate taxonomy of APC subsets found in both mouse and human skin. It also examines the functional specificity of individual APC subsets and their collaboration with other immune cell types that together promote adaptive T cell and regional cutaneous immune responses during homeostasis, inflammation, and disease.

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“…It is plausible that a subset of CD1-reactive T cells are functional counterparts of the dendritic epidermal T cells (DETCs) in mice. However, low CD1a expression has not been reported to be associated with susceptibility to skin diseases, suggesting functional redundancy (124,125). However, elevated CD1-reactive responses may represent therapeutic targets.…”

Section: Cd1-reactive T Cells and The Skinmentioning

confidence: 99%

Innate Lymphocyte Mechanisms in Skin Diseases

Chen

Hardman

Yadava

et al. 2020

Annu. Rev. Immunol.

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Innate lymphocyte populations are emerging as key effectors in tissue homeostasis, microbial defense, and inflammatory skin disease. The cells are evolutionarily ancient and carry conserved principles of function, which can be achieved through shared or unique specific mechanisms. Recent technological and treatment advances have provided insight into heterogeneity within and between individuals and species. Similar pathways can extend through to adaptive lymphocytes, which softens the margins with innate lymphocyte populations and allows investigation of nonredundant pathways of immunity and inflammation that might be amenable to therapeutic intervention. Here, we review advances in understanding of innate lymphocyte biology with a focus on skin disease and the roles of commensal and pathogen responses and tissue homeostasis.

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Complete human CD1a deficiency on Langerhans cells due to a rare point mutation in the coding sequence

Cited by 4 publications

References 19 publications

CD1a promotes systemic manifestations of skin inflammation

CD1a promotes systemic manifestations of skin inflammation

Antigen-Presenting Cells in the Skin

Innate Lymphocyte Mechanisms in Skin Diseases

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