TGFβ1 overexpression by keratinocytes alters skin dendritic cell homeostasis and enhances contact hypersensitivity

Javed Mohammed; Andrew J. Gunderson; Hong Hanh Khong; Richard D. Koubek; Mark C. Udey; Adam B. Glick

doi:10.1038/jid.2012.241

TGFβ1 overexpression by keratinocytes alters skin dendritic cell homeostasis and enhances contact hypersensitivity

Javed Mohammed, Andrew J. Gunderson, Hong Hanh Khong, Richard D. Koubek, Mark C. Udey, Adam B. Glick

Dermatology

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

Overexpression of transforming growth factor beta-1 (TGFβ1) in mouse epidermis causes cutaneous inflammation and keratinocyte hyperproliferation. Here we examined acute effects of TGFβ1 overproduction by keratinocytes on skin dendritic cells (DCs). TGFβ1 induction for 2 and 4 days increased the numbers and CD86 expression of B220 + plasmacytoid DCs (pDCs) and CD207 + CD103 +, CD207 - CD103 - CD11b +, and CD207 - CD103 - CD11b - dermal DCs (dDCs) in skin-draining lymph nodes (SDLNs). The dermis of TGFβ1-overexpressing mice had significantly more pDCs, CD207 + CD103 + dDCs, and CD207 - CD11b + dDCs in the absence of increased dermal proliferation. Application of dye, tetramethyl rhodamine iso-thiocyanate (TRITC), in dibutylpthalate (DBP) solution after TGFβ1 induction increased the numbers of TRITC + CD207 - dDCs in SDLNs, and augmented TRITC/DBP-induced Langerhans cell (LC) migration 72 hours post TRITC treatment. Consistent with this, LC migration was increased in vitro by TGFβ1 overexpression in skin explants and by exogenous TGFβ1 in culture media. Transient TGFβ1 induction during DNFB sensitization increased contact hypersensitivity responses by 1.5-fold. Thus, elevated epidermal TGFβ1 alone is sufficient to alter homeostasis of multiple cutaneous DC subsets, and enhance DC migration and immune responses to contact sensitizers. These results highlight a role for keratinocyte-derived TGFβ1 in DC trafficking and in the initiation of skin inflammation.

Original language	English (US)
Pages (from-to)	135-143
Number of pages	9
Journal	Journal of Investigative Dermatology
Volume	133
Issue number	1
DOIs	https://doi.org/10.1038/jid.2012.241
State	Published - Jan 2013

Bibliographical note

Funding Information:
We thank Dr Maria Gaiser for suggestions and technical help, and the Huck Institute Flow Cytometry Core Facility for help with flow cytometry. This study was funded by grants CA117957 and 122109 (AG) from the NCI and by the Intramural Research Program of the NIH, Center for Cancer Research, NCI (MCU).

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title = "TGFβ1 overexpression by keratinocytes alters skin dendritic cell homeostasis and enhances contact hypersensitivity",

abstract = "Overexpression of transforming growth factor beta-1 (TGFβ1) in mouse epidermis causes cutaneous inflammation and keratinocyte hyperproliferation. Here we examined acute effects of TGFβ1 overproduction by keratinocytes on skin dendritic cells (DCs). TGFβ1 induction for 2 and 4 days increased the numbers and CD86 expression of B220 + plasmacytoid DCs (pDCs) and CD207 + CD103 +, CD207 - CD103 - CD11b +, and CD207 - CD103 - CD11b - dermal DCs (dDCs) in skin-draining lymph nodes (SDLNs). The dermis of TGFβ1-overexpressing mice had significantly more pDCs, CD207 + CD103 + dDCs, and CD207 - CD11b + dDCs in the absence of increased dermal proliferation. Application of dye, tetramethyl rhodamine iso-thiocyanate (TRITC), in dibutylpthalate (DBP) solution after TGFβ1 induction increased the numbers of TRITC + CD207 - dDCs in SDLNs, and augmented TRITC/DBP-induced Langerhans cell (LC) migration 72 hours post TRITC treatment. Consistent with this, LC migration was increased in vitro by TGFβ1 overexpression in skin explants and by exogenous TGFβ1 in culture media. Transient TGFβ1 induction during DNFB sensitization increased contact hypersensitivity responses by 1.5-fold. Thus, elevated epidermal TGFβ1 alone is sufficient to alter homeostasis of multiple cutaneous DC subsets, and enhance DC migration and immune responses to contact sensitizers. These results highlight a role for keratinocyte-derived TGFβ1 in DC trafficking and in the initiation of skin inflammation.",

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AU - Udey, Mark C.

AU - Glick, Adam B.

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TGFβ1 overexpression by keratinocytes alters skin dendritic cell homeostasis and enhances contact hypersensitivity

Abstract

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