CD49a Expression Defines Tissue-Resident CD8+ T Cells Poised for Cytotoxic Function in Human Skin

By S. Cheuk, Heinrich Schlums, I. Gallais Sérézal, E. Martini, S. Chiang, N. Marquardt, Anna Gibbs, Ebba Detlofsson, A. Introini, Marianne Forkel and 10 more. Immunity, 2017

612 citations recorded by the source corpus.

SUMMARY Tissue‐resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8+ Trm cells on a compartmental and functional basis. In human skin epithelia, CD8+CD49a+ Trm cells produced interferon‐&ggr;, whereas CD8+CD49a− Trm cells produced interleukin‐17 (IL‐17). In addition, CD8+CD49a+ Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL‐15, thereby promoting a strong cytotoxic response. In skin from patients with vitiligo, where melanocytes are eradicated locally, CD8+CD49a+ Trm cells that constitutively expressed perforin and granzyme B accumulated both in the epidermis and dermis. Conversely, CD8+CD49a– Trm cells from psoriasis lesions predominantly generated IL‐17 responses that promote local inflammation in this skin disease. Overall, CD49a expression delineates CD8+ Trm cell specialization in human epithelial barriers and correlates with the effector cell balance found in distinct inflammatory skin diseases. Graphical Abstract Figure. No Caption available. HighlightsCD49a expression marks CD8+ Trm cells poised for IFN‐&ggr; production in human skinIL‐15 drives potent cytotoxic capacity in CD49a+ Trm cellsIL‐17 is preferentially produced by CD49a− CD8+ Trm cells in the skinCD49a+ versus CD49‐ Trm cell functional dichotomy is preserved in vitiligo and psoriasis &NA; Tissue‐resident memory T (Trm) cells provide localized adaptive immunity in peripheral tissues. Cheuk et al. identify cytotoxic CD49a+CD8+ Trm cells and IL‐17‐producing CD49a−CD8+ Trm cells in healthy human skin. The functional dichotomy of pathogenic Trm cells based on CD49a expression is preserved in focal skin diseases vitiligo and psoriasis.

Subfields: Cell Biology, Dermatology, Immunology

View Paper: https://www.semanticscholar.org/paper/f4673a54b34b9dc770ae33f0d887e4d44a057e59

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. Miriam Merad
2. Brahma V. Kumar
3. Judy H. Cho
4. D. Farber

Citations in the corpus

• Single-Cell Analysis of Crohn’s Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy (2019, background): “Two of these clusters were highly enriched for the cytotoxic program (#26, 4), thus reminiscent of the Trm poised for cytotoxic functions recently described in the skin (Cheuk et al., 2017).”
• Human T cell development, localization, and function throughout life (2018, background): “A recent study examining Trm cells from human skin found that the CD49a+CD103+ subset of CD8+ Trm cells represented a subset with superior cytotoxic abilities compared with CD49a− counterparts (Cheuk et al., 2017).”
• Human tissue-resident memory T cells are defined by core transcriptional and functional signatures in lymphoid and mucosal sites (2017, background): “In human studies, CD8 TRMs isolated based on CD103 expression from individual tissues (lung and skin) have been profiled in comparison to blood subsets (Cheuk et al., 2017; Hombrink et al., 2016).”