Cutting Edge: Dendritic Epidermal γδ T Cell Ligands Are Rapidly and Locally Expressed by Keratinocytes following Cutaneous Wounding

Komori, H. Kiyomi; Witherden, Deborah A.; Kelly, Ryan; Sendaydiego, Kevin; Jameson, Julie; Teyton, Luc; Havran, Wendy L.

doi:10.4049/jimmunol.1100887

Cited by 80 publications

(84 citation statements)

References 25 publications

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“…The TRGV5 gene rearrangement detected in our study corresponds to that reported for the previously described invariant Vγ5 + dendritic epidermal T cells (DETCs) (43,44). DETCs are the most common skin-resident γδ T cell population and have been reported to recognize a stress-induced self-antigen derived from keratinocytes (46,47). In contrast, the TRGV6 gene rearrangement described herein corresponds to that reported for canonical γδ T cells residing in the liver, placenta, kidney, uterus, tongue and other mucosal sites (33,45).…”

Section: Trgj1*01supporting

confidence: 57%

“…Multiple gene rearrangements encoding for the same CDR3 aa sequence, as reported here, favor antigen specificity as the driving force behind the observed pathogen-induced T cell expansion. Although it is unclear whether the γδ T cell TCR reactivity was against a yet-tobe-described S. aureus-derived antigen or self-antigen as previously postulated (46,47), it is clear that this distinctive TRGV5/ V6-encoded CDR3 aa sequence is critical for mediating robust immune protection against pathogens at the skin and potentially other barrier sites. Furthermore, the TRGV5 and TRGV6 CDR3-encoding sequences correlated with TBX21 expression, providing an explanation for increased γδ T cell production of TNF/IFN-γ.…”

Section: Trgj1*01mentioning

confidence: 99%

See 1 more Smart Citation

Clonally expanded γδ T cells protect against Staphylococcus aureus skin reinfection

Dillen

Pinsker

Marusina³

et al. 2018

Journal of Clinical Investigation

112

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Section: Trgj1*01supporting

confidence: 57%

Section: Trgj1*01mentioning

confidence: 99%

Clonally expanded γδ T cells protect against Staphylococcus aureus skin reinfection

Dillen

Pinsker

Marusina³

et al. 2018

Journal of Clinical Investigation

112

View full text Add to dashboard Cite

“…DETC play an essential role in wound repair (21), and therefore, we sought to determine whether DETC are the source of IL-17A in the epidermal compartment. We reasoned that direct TCR ligation would be critical for IL-17A production by DETC, because DETC become activated through their TCR by recognition of self antigens expressed on wounded keratinocytes (25,42). Indeed, we observed that freshly isolated and sorted Vγ3 + DETC stimulated with anti-CD3ε strongly induced IL-17A mRNA and protein ( Figure 2, A and B).…”

Section: Introductionmentioning

confidence: 85%

Dendritic epidermal T cells regulate skin antimicrobial barrier function

MacLeod¹,

Hemmers²,

Garijo³

et al. 2013

J. Clin. Invest.

Self Cite

127

166

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“…Tightly interspersed with the epidermal LC network in mice is a similarly dense network of DETCs (13). These T cells are important for efficient wound repair and respond to signals from stimulated keratinocytes (14,15). Similarly, populations of epidermal T cells are also present in humans and may also contribute to wound repair (16).…”

Section: Resultsmentioning

confidence: 99%

Persistence of skin-resident memory T cells within an epidermal niche

Zaid

Mackay

Rahimpour

et al. 2014

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

267

310

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Barrier tissues such as the skin contain various populations of immune cells that contribute to protection from infections. These include recently identified tissue-resident memory T cells (T RM ). In the skin, these memory CD8 + T cells reside in the epidermis after being recruited to this site by infection or inflammation. In this study, we demonstrate prolonged persistence of epidermal T RM preferentially at the site of prior infection despite sustained migration. Computational simulation of T RM migration within the skin over long periods revealed that the slow rate of random migration effectively constrains these memory cells within the region of skin in which they form. Notably, formation of T RM involved a concomitant local reduction in dendritic epidermal γδ T-cell numbers in the epidermis, indicating that these populations persist in mutual exclusion and may compete for local survival signals. Accordingly, we show that expression of the aryl hydrocarbon receptor, a transcription factor important for dendritic epidermal γδ T-cell maintenance in skin, also contributes to the persistence of skin T RM . Together, these data suggest that skin tissue-resident memory T cells persist within a tightly regulated epidermal T-cell niche. T he skin is a complex organ that acts as a primary barrier between the body and the environment. Multiple leukocyte subsets reside within the main compartments of the skin, the dermis and the epidermis, as well as the hair follicles that are contiguous with the epidermis. Populations of macrophages, dendritic cells, mast cells, γδ T cells and αβ T cells are present in the dermis, and Langerhans cells (LCs) and dendritic epidermal γδ T cells (DETCs) lie in a strategic network in the epidermis (1). We recently described a population of memory CD8 + T cells that enter the epidermis and hair follicles during infection or inflammation and become long-lived populations of tissue-resident memory T cells (T RM ) (2-5). These memory T cells are sequestered in this site and are distinct from circulating effector memory (T EM ) and central memory (T CM ) populations (3, 6). Memory CD8 + T cells in the epidermis display a dendritic morphology and move at a slower velocity than T cells within the dermis. These memory T cells are sequestered in the skin epithelial layer and do not recirculate to other tissues. In contrast, memory CD4 + T cells are found within the dermis and at least a proportion of these cells are capable of recirculating around the body (3, 7).In this study, we sought to further examine the mechanisms of T RM persistence within the skin. We reveal that skin T RM persist at the site of their formation and despite displaying a sustained mode of random migration, the slow rate of this movement locally constrains these memory cells. Examination of other cells in this environment showed that although epidermal T RM regularly interact with LC, these interactions were not required for persistence. In contrast, skin tissue-resident memory T cells replaced DETCs in the epidermis, seem...

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Cutting Edge: Dendritic Epidermal γδ T Cell Ligands Are Rapidly and Locally Expressed by Keratinocytes following Cutaneous Wounding

Cited by 80 publications

References 25 publications

Clonally expanded γδ T cells protect against Staphylococcus aureus skin reinfection

Clonally expanded γδ T cells protect against Staphylococcus aureus skin reinfection

Dendritic epidermal T cells regulate skin antimicrobial barrier function

Persistence of skin-resident memory T cells within an epidermal niche

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