IL-13 from intraepithelial lymphocytes regulates tissue homeostasis and protects against carcinogenesis in the skin

Dalessandri, Tim; Crawford, Greg; Hayes, Michael; Seoane, Rocio Castro; Strid, Jessica

doi:10.1038/ncomms12080

Cited by 70 publications

(75 citation statements)

References 65 publications

(81 reference statements)

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“…Thus, HPV oncoprotein-induced down-regulation of Skint1 can provide an explanation for the change in DETC morphology and for their reduction in density within the epidermis. DETCs may play an antitumor role via killing of tumor cells (5) or, as shown more recently in vivo, by tissue regulation of the epithelial barrier via IL-13 (43). The reduction of a particular (protumor) γδ T-cell subset from the epithelial barrier via the decreased expression of the corresponding Btnl member can provide a mechanism to evade the γδ T-cell subset that normally would provide tumor immunosurveillance at the epithelial barrier.…”

Section: Discussionmentioning

confidence: 98%

Human papillomavirus oncoproteins induce a reorganization of epithelial-associated γδ T cells promoting tumor formation

hede

Polese

Humblet

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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It has been shown that γδ T cells protect against the formation of squamous cell carcinoma (SCC) in several models. However, the role of γδ T cells in human papillomavirus (HPV)-associated uterine cervical SCC, the third-leading cause of death by cancer in women, is unknown. Here, we investigated the impact of γδ T cells in a transgenic mouse model of carcinogenesis induced by HPV16 oncoproteins. Surprisingly, γδ T cells promoted the development of HPV16 oncoprotein-induced lesions. HPV16 oncoproteins induced a decrease in epidermal Skint1 expression and the associated antitumor Vγ5 γδ T cells, which were replaced by γδ T-cell subsets (mainly Vγ6 γδCCR2CCR6) actively producing IL-17A. Consistent with a proangiogenic role, γδ T cells promoted the formation of blood vessels in the dermis underlying the HPV-induced lesions. In human cervical biopsies, IL-17A γδ T cells could only be observed at the cancer stage (SCC), where HPV oncoproteins are highly expressed, supporting the clinical relevance of our observations in mice. Overall, our results suggest that HPV16 oncoproteins induce a reorganization of the local epithelial-associated γδ T-cell subpopulations, thereby promoting angiogenesis and cancer development.

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Section: Discussionmentioning

confidence: 98%

Human papillomavirus oncoproteins induce a reorganization of epithelial-associated γδ T cells promoting tumor formation

hede

Polese

Humblet

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…2 ). Intraepithelial resident γδ T cells were recently reported as potent producers of IL-13 ( 35 ). Furthermore, a significant upregulation of IL-13 protein expression was demonstrated in subacute and chronic AD skin lesions ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanism of Atopic Dermatitis Induction Following Sensitization and Challenge with 2,4-Dinitrochlorobenzene in Mouse Skin Tissue

et al. 2018

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Laboratory animal models have been developed to investigate preventive or therapeutic effect of medicinal products, or occurrence or progression mechanism of atopic dermatitis (AD), a pruritic and persistent inflammatory skin disease. The murine model with immunologic phenomena resembling human AD was introduced, which demonstrated skewedness toward predominance of type-2 helper T cell reactivity and pathophysiological changes similar as human AD following 2,4-dinitrochlorobenzene (DNCB) sensitization and challenge. Molecular mechanism on the DNCB-mediated AD was further evaluated. Skin tissues were collected from mice treated with DNCB, and each tissue was equally divided into two sections; one for protein and the other for mRNA analysis. Expression of filaggrin, an important protein for keratinocyte integrity, was evaluated through SDS-PAGE. Level of mRNA expression for cytokines was determined through semi-quantitative reverse transcriptase polymerase chain reaction. Expression of filaggrin protein was significantly enhanced in the mice treated with DNCB compared with the vehicle (acetone : olive oil = 4 : 1 mixture) treatment group or the normal group without any treatment. Level of tumor necrosis factor-alpha and interleukin-18 mRNA expression, cytokines involved in activity of type-1 helper T (TH1) cell, was significantly downregulated in the AD group compared with other control groups. These results suggest that suppression of TH1 cell-mediated immune response could be reflected into the skin tissue of mice treated with DNCB for AD induction, and disturbance of keratinocyte integrity might evoke a compensatory mechanism.

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“…In mice, γδ T cells protect the skin from tumors by responding to increased expression of the MICA homologue Rae1 [25]. Remarkably, this protective contribution not only involves direct cytotoxicity, but also the production of interleukin (IL)-13 [26] and modulation of B cells promoting immunoglobulin E class switching and the accumulation of autoreactive antibodies [27]. Mice lacking NKG2D show more susceptibility to spontaneous development of prostate cancer [28], and T cells and NK cells rapidly clear malignant cells injected into mice when they express NKG2D ligands [29].…”

Section: Self-surveillance Natural Killer Receptor Nkg2d and Other Ncrsmentioning

confidence: 99%

The emerging role of γδ T cells in cancer immunotherapy

Nussbaumer¹,

Koslowski²

2019

Immuno-Oncology Technology

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The recent successes of chimeric antigen receptor T cells in the treatment of hematological malignancies have clearly led to an explosion in the field of adoptive cell therapy for cancer. Current efforts are focused on the translation of this exciting technology to the treatment of solid tumors and the development of allogeneic 'off-theshelf' therapies. γδ T cells are currently gaining considerable attention in this field as their unique biology and established role in cancer immunosurveillance place them in a unique position to potentially overcome these challenges in adoptive cell therapy. Here, we review the relevant aspects of the function of γδ T cells in cancer immunity, and summarize clinical observations and clinical trial results that highlight their emerging role as a platform for the development of safe and effective cancer immunotherapies.

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IL-13 from intraepithelial lymphocytes regulates tissue homeostasis and protects against carcinogenesis in the skin

Cited by 70 publications

References 65 publications

Human papillomavirus oncoproteins induce a reorganization of epithelial-associated γδ T cells promoting tumor formation

Human papillomavirus oncoproteins induce a reorganization of epithelial-associated γδ T cells promoting tumor formation

Molecular Mechanism of Atopic Dermatitis Induction Following Sensitization and Challenge with 2,4-Dinitrochlorobenzene in Mouse Skin Tissue

The emerging role of γδ T cells in cancer immunotherapy

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