Self-Antigen Presentation by Keratinocytes in the Inflamed Adult Skin Modulates T-Cell Auto-Reactivity

Meister, Michael T.; Tounsi, Amel; Gaffal, Evelyn; Bald, Tobias; Papatriantafyllou, Maria; Ludwig, Julia; Pougialis, Georg; Bestvater, Felix; Klotz, Luisa; Moldenhauer, Gerhard; Tüting, Thomas; Hämmerling, Günter J.; Arnold, Bernd; Oelert, Thilo

doi:10.1038/jid.2015.130

Cited by 20 publications

(14 citation statements)

References 31 publications

(39 reference statements)

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“…We have recently demonstrated that DKK3 can act as a tissue-derived immune modulator that influences type and strength of local T cell responses in models of peripheral tolerance, transplantation, and autoimmune disease (27)(28)(29). We have found that DKK3 is expressed during kidney development, which occurs by a mesenchymal-epithelial transition.…”

Section: Introductionmentioning

confidence: 89%

Tubular Dickkopf-3 promotes the development of renal atrophy and fibrosis

Federico¹,

Meister

Mathow³

et al. 2016

JCI Insight

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Section: Introductionmentioning

confidence: 89%

Tubular Dickkopf-3 promotes the development of renal atrophy and fibrosis

Federico¹,

Meister

Mathow³

et al. 2016

JCI Insight

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“…However, MHC class II expression can also be induced on other cells, 96 including keratinocytes, by IFNγ 97‐99 . Keratinocytes expressing MHC class II can successfully present antigen epitopes to CD4 + T cells, 100,101 although it is unclear at what level of efficacy this actually occurs in human skin in vivo.…”

Section: Mechanisms Of Hf Ipmentioning

confidence: 99%

Hair follicle immune privilege and its collapse in alopecia areata

Bertolini

McElwee

Gilhar

et al. 2020

Experimental Dermatology

166

157

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Anagen stage hair follicles (HFs) exhibit “immune privilege (IP)” from the level of the bulge downwards to the bulb. Both passive and active IP mechanisms protect HFs from physiologically undesired immune responses and limit immune surveillance. IP is relative, not absolute, and is primarily based on absent, or greatly reduced, intra‐follicular antigen presentation via MHC class I and II molecules, along with prominent expression of “no danger” signals like CD200 and the creation of an immunoinhibitory signalling milieu generated by the secretory activities of HFs. Perifollicular mast cells, Tregs and other immunocytes may also contribute to HF IP maintenance in healthy human skin. Collapse of anagen hair bulb IP is an essential prerequisite for the development of alopecia areata (AA). In AA, lesional HFs are rapidly infiltrated by NKG2D + T cells and natural killer (NK) cells, while perifollicular mast cells acquire a profoundly pro‐inflammatory phenotype and interact with autoreactive CD8+ T cells. Using animal models, significant functional evidence has accumulated that demonstrates the dominance of the immune system in AA pathogenesis. Purified CD8+T‐cell and NK cell populations alone, which secrete fγ, suffice to induce the AA phenotype, while CD4+T‐cells aggravate it, and Tregs and iNKT cells may provide relative protection against AA development. While IP collapse may be induced by exogenous agents, inherent IP deficiencies might confer increased susceptibility to AA for some individuals. Thus, a key goal for effective AA management is the re‐establishment of a functional HF IP, which will also provide superior protection from disease relapse.

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“…In addition, DKK3 expression was found in human MSCs ( 18 , 19 ). We recently identified DKK3 as a novel immune-mediator limiting CD8 + and CD4 + T cell-mediated responses ( 20 – 22 ). In a transgenic mouse model of peripheral T cell tolerance, we showed that CD8 + T cells, which were neonatally tolerized toward a self-antigen exclusively expressed on keratinocytes, expressed DKK3.…”

Section: Introductionmentioning

confidence: 99%

Dickkopf-3 Contributes to the Regulation of Anti-Tumor Immune Responses by Mesenchymal Stem Cells

Tounsi

Shridhar

et al. 2015

Front. Immunol.

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Mesenchymal stem cells (MSCs) are known to limit immune responses in vivo by multiple soluble factors. Dickkopf-3 (DKK3), a secreted glycoprotein, has recently been identified as a novel immune modulator. Since DKK3 has been reported to be produced by MSCs, we investigated whether DKK3 contributes to the immune suppression of anti-tumor responses by MSCs. Whereas wild-type MSCs inhibited immune responses against two different transplantation tumors, DKK3-deficient MSCs did not affect the rejection process. Increased CD8+ T cell and reduced M2-type macrophages infiltration was observed in tumors inoculated together with DKK3-deficient MSCs. Thus, DKK3 could alter the composition of the tumor stroma, thereby supporting the MSCs-mediated suppression of immune responses against these tumor transplants.

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Self-Antigen Presentation by Keratinocytes in the Inflamed Adult Skin Modulates T-Cell Auto-Reactivity

Cited by 20 publications

References 31 publications

Tubular Dickkopf-3 promotes the development of renal atrophy and fibrosis

Tubular Dickkopf-3 promotes the development of renal atrophy and fibrosis

Hair follicle immune privilege and its collapse in alopecia areata

Dickkopf-3 Contributes to the Regulation of Anti-Tumor Immune Responses by Mesenchymal Stem Cells

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