Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Tissue-resident memory T cells in the skin

  • 209 Accesses



Tissue-resident memory T (TRM) cells are a newly described subset of memory T cells. The best characterized TRM cells are CD8+ and express CD103 and CD69. These cells are non-recirculating and persist long term in tissues, providing immediate protection against invading pathogens. However, their inappropriate activation might contribute to the pathogenesis of autoimmune and inflammatory disorders. In the skin, these cells have been described in psoriasis, vitiligo, and melanoma among other diseases.


Literature review was done to highlight what is currently known on the phenotype and function of TRM cells and summarizes the available data describing their role in various cutaneous conditions.


Resolved psoriatic skin and disease-naïve non-lesional skin contain a population of IL-17-producing TRM cells with shared receptor sequences that recognize common antigens and likely contribute to disease recurrence after cessation of therapy. In vitiligo, TRM cells produce perforin, granzyme B, and interferon-γ following stimulation by interleukin-15 and collaborate with recirculating memory T cells to maintain disease. In melanoma, increased accumulation of TRM cells was recently shown to correlate with improved survival in patients undergoing therapy with immune checkpoint inhibitors.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2


  1. 1.

    Takamura S. Niches for the long-term maintenance of tissue-resident memory T cells. Front Immunol. 2018;9:1214. https://doi.org/10.3389/fimmu.2018.01214.

  2. 2.

    Wu H, Liao W, Li Q, Long H, Yin H, Zhao M, et al. Pathogenic role of tissue-resident memory T cells in autoimmune diseases. Autoimmun Rev. 2018;17(9):906–11. https://doi.org/10.1016/j.autrev.2018.03.014.

  3. 3.

    Clark RA, Chong B, Mirchandani N, Brinster NK, Yamanaka K, Dowgiert RK, et al. The vast majority of CLA+ T cells are resident in normal skin. J Immunol. 2006;176(7):4431–9.

  4. 4.

    Mueller SN, Zaid A, Carbone FR. Tissue-resident T cells: dynamic players in skin immunity. Front Immunol. 2014;5:332. https://doi.org/10.3389/fimmu.2014.00332.

  5. 5.

    Corgnac S, Boutet M, Kfoury M, Naltet C, Mami-Chouaib F. The emerging role of CD8(+) tissue resident memory T (TRM) cells in antitumor immunity: a unique functional contribution of the CD103 integrin. Front Immunol. 2018;9:1904. https://doi.org/10.3389/fimmu.2018.01904.

  6. 6.

    Mackay LK, Braun A, Macleod BL, Collins N, Tebartz C, Bedoui S, et al. Cutting edge: CD69 interference with sphingosine-1-phosphate receptor function regulates peripheral T cell retention. J Immunol. 2015;194(5):2059–63. https://doi.org/10.4049/jimmunol.1402256.

  7. 7.

    Mackay LK, Rahimpour A, Ma JZ, Collins N, Stock AT, Hafon ML, et al. The developmental pathway for CD103(+)CD8+ tissue-resident memory T cells of skin. Nat Immunol. 2013;14(12):1294–301. https://doi.org/10.1038/ni.2744.

  8. 8.

    Cheuk S, Schlums H, Gallais Sérézal I, Martini E, Chiang SC, Marquardt N, et al. CD49a expression defines tissue-resident CD8(+) T cells poised for cytotoxic function in human skin. Immunity. 2017;46(2):287–300. https://doi.org/10.1016/j.immuni.2017.01.009.

  9. 9.

    Seidel JA, Vukmanovic-Stejic M, Muller-Durovic B, Patel N, Fuentes-Duculan J, Henson SM, et al. Skin resident memory CD8(+) T cells are phenotypically and functionally distinct from circulating populations and lack immediate cytotoxic function. Clin Exp Immunol. 2018;194(1):79–92. https://doi.org/10.1111/cei.13189.

  10. 10.

    Topham DJ, Reilly EC. Tissue-resident memory CD8(+) T cells: from phenotype to function. Front Immunol. 2018;9:515. https://doi.org/10.3389/fimmu.2018.00515.

  11. 11.

    Glennie ND, Volk SW, Scott P. Skin-resident CD4+ T cells protect against Leishmania major by recruiting and activating inflammatory monocytes. PLoS Pathog. 2017;13(4):e1006349. https://doi.org/10.1371/journal.ppat.1006349.

  12. 12.

    Park CO, Fu X, Jiang X, Pan Y, Teague JE, Collins N, et al. Staged development of long-lived T-cell receptor alphabeta TH17 resident memory T-cell population to Candida albicans after skin infection. J Allergy Clin Immunol. 2018;142(2):647–62. https://doi.org/10.1016/j.jaci.2017.09.042.

  13. 13.

    Cheuk S, Wiken M, Blomqvist L, Nylen S, Talme T, Stahle M, et al. Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis. J Immunol. 2014;192(7):3111–200. https://doi.org/10.4049/jimmunol.1302313.

  14. 14.

    Mackay LK, Wynne-Jones E, Freestone D, Pellicci DG, Mielke LA, Newman DM, et al. T-box transcription factors combine with the cytokines TGF-beta and IL-15 to control tissue-resident memory T cell fate. Immunity. 2015;43(6):1101–11. https://doi.org/10.1016/j.immuni.2015.11.008.

  15. 15.

    Sowell RT, Rogozinska M, Nelson CE, Vezys V, Marzo AL. Cutting edge: generation of effector cells that localize to mucosal tissues and form resident memory CD8 T cells is controlled by mTOR. J Immunol. 2014;193(5):2067–71. https://doi.org/10.4049/jimmunol.1400074.

  16. 16.

    Balato ADCR, Lembo S, Mattii M, Megna M, Schiattarella M, et al. Mammalian target of rapamycin in inflammatory skin conditions. Eur J Inflam. 2014;12(2):341–50.

  17. 17.

    Buerger C. Epidermal mTORC1 signaling contributes to the pathogenesis of psoriasis and could serve as a therapeutic target. Front Immunol. 2018;9:2786. https://doi.org/10.3389/fimmu.2018.02786.

  18. 18.

    Mackay LK, Minnich M, Kragten NA, Liao Y, Nota B, Seillet C, et al. Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes. Science. 2016;352(6284):459–63. https://doi.org/10.1126/science.aad2035.

  19. 19.

    Milner JJ, Toma C, Yu B, Zhang K, Omilusik K, Phan AT, et al. Runx3 programs CD8(+) T cell residency in non-lymphoid tissues and tumours. Nature. 2017;552(7684):253–7. https://doi.org/10.1038/nature24993.

  20. 20.

    Hombrink P, Helbig C, Backer RA, Piet B, Oja AE, Stark R, et al. Programs for the persistence, vigilance and control of human CD8(+) lung-resident memory T cells. Nat Immunol. 2016;17(12):1467–78. https://doi.org/10.1038/ni.3589.

  21. 21.

    Zaid A, Mackay LK, Rahimpour A, Braun A, Veldhoen M, Carbone FR, et al. Persistence of skin-resident memory T cells within an epidermal niche. Proc Natl Acad Sci USA. 2014;111(14):5307–12. https://doi.org/10.1073/pnas.1322292111.

  22. 22.

    Zhou X, Yu S, Zhao DM, Harty JT, Badovinac VP, Xue HH. Differentiation and persistence of memory CD8(+) T cells depend on T cell factor 1. Immunity. 2010;33(2):229–40. https://doi.org/10.1016/j.immuni.2010.08.002.

  23. 23.

    Ma L, Xue H, Gao T, Gao M, Zhang Y. Notch1 signaling regulates the Th17/Treg immune imbalance in patients with psoriasis vulgaris. Mediators Inflamm. 2018;2018:3069521. https://doi.org/10.1155/2018/3069521.

  24. 24.

    Furue M, Hashimoto-Hachiya A, Tsuji G. Aryl hydrocarbon receptor in atopic dermatitis and psoriasis. Int J Mol Sci. 2019. https://doi.org/10.3390/ijms20215424.

  25. 25.

    Ariotti S, Beltman JB, Chodaczek G, Hoekstra ME, van Beek AE, Gomez-Eerland R, et al. Tissue-resident memory CD8+ T cells continuously patrol skin epithelia to quickly recognize local antigen. Proc Natl Acad Sci USA. 2012;109(48):19739–44. https://doi.org/10.1073/pnas.1208927109.

  26. 26.

    Collins N, Jiang X, Zaid A, Macleod BL, Li J, Park CO, et al. Skin CD4(+) memory T cells exhibit combined cluster-mediated retention and equilibration with the circulation. Nat Commun. 2016;7:11514. https://doi.org/10.1038/ncomms11514.

  27. 27.

    Hartana CA, Bergman EA, Broome A, Berglund S, Johansson M, Alamdari F, et al. Tissue-resident memory T cells are epigenetically cytotoxic with signs of exhaustion in human urinary bladder cancer. Clin Exp Immunol. 2018;194(1):39–533. https://doi.org/10.1111/cei.13183.

  28. 28.

    Steinbach K, Vincenti I, Kreutzfeldt M, Page N, Muschaweckh A, Wagner I, et al. Brain-resident memory T cells represent an autonomous cytotoxic barrier to viral infection. J Exp Med. 2016;213(8):1571–87. https://doi.org/10.1084/jem.20151916.

  29. 29.

    Mackay LK, Stock AT, Ma JZ, Jones CM, Kent SJ, Mueller SN, et al. Long-lived epithelial immunity by tissue-resident memory T (TRM) cells in the absence of persisting local antigen presentation. Proc Natl Acad Sci USA. 2012;109(18):7037–42. https://doi.org/10.1073/pnas.1202288109.

  30. 30.

    Ariotti S, Hogenbirk MA, Dijkgraaf FE, Visser LL, Hoekstra ME, Song JY, et al. T cell memory. Skin-resident memory CD8(+) T cells trigger a state of tissue-wide pathogen alert. Science. 2014;346(6205):101–5. https://doi.org/10.1126/science.1254803.

  31. 31.

    Pizzolla A, Nguyen THO, Smith JM, Brooks AG, Kedzieska K, Heath WR, et al. Resident memory CD8(+) T cells in the upper respiratory tract prevent pulmonary influenza virus infection. Sci Immunol. 2017. https://doi.org/10.1126/sciimmunol.aam6970.

  32. 32.

    Park SL, Zaid A, Hor JL, Christo SN, Prier JE, Davies B, et al. Local proliferation maintains a stable pool of tissue-resident memory T cells after antiviral recall responses. Nat Immunol. 2018;19(2):183–91. https://doi.org/10.1038/s41590-017-0027-5.

  33. 33.

    Beura LK, Mitchell JS, Thompson EA, Schenkel JM, Mohammed J, Wijeyesinghe S, et al. Intravital mucosal imaging of CD8(+) resident memory T cells shows tissue-autonomous recall responses that amplify secondary memory. Nat Immunol. 2018;19(2):173–82. https://doi.org/10.1038/s41590-017-0029-3.

  34. 34.

    Shiohara T, Mizukawa Y, Teraki Y. Pathophysiology of fixed drug eruption: the role of skin-resident T cells. Curr Opin Allergy Clin Immunol. 2002;2(4):317–23.

  35. 35.

    Teraki Y, Shiohara T. IFN-gamma-producing effector CD8+ T cells and IL-10-producing regulatory CD4+ T cells in fixed drug eruption. J Allergy Clin Immunol. 2003;112(3):609–15.

  36. 36.

    Komatsu T, Moriya N, Shiohara T. T cell receptor (TCR) repertoire and function of human epidermal T cells: restricted TCR V alpha-V beta genes are utilized by T cells residing in the lesional epidermis in fixed drug eruption. Clin Exp Immunol. 1996;104(2):343–50.

  37. 37.

    Boyman O, Hefti HP, Conrad C, Nickoloff BJ, Suter M, Nestle FO. Spontaneous development of psoriasis in a new animal model shows an essential role for resident T cells and tumor necrosis factor-alpha. J Exp Med. 2004;199(5):731–6. https://doi.org/10.1084/jem.20031482.

  38. 38.

    Suarez-Farinas M, Fuentes-Duculan J, Lowes MA, Krueger JG. Resolved psoriasis lesions retain expression of a subset of disease-related genes. J Invest Dermatol. 2011;131(2):391–400. https://doi.org/10.1038/jid.2010.280.

  39. 39.

    Torres-Alvarez B, Castanedo-Cazares JP, Fuentes-Ahumada C, Moncada B. The effect of methotrexate on the expression of cell adhesion molecules and activation molecule CD69 in psoriasis. J Eur Acad Dermatol Venereol. 2007;21(3):334–9. https://doi.org/10.1111/j.1468-3083.2006.01916.x.

  40. 40.

    Matos TR, O'Malley JT, Lowry EL, Hamm D, Kirsch IR, Robins HS, et al. Clinically resolved psoriatic lesions contain psoriasis-specific IL-17-producing alphabeta T cell clones. J Clin Invest. 2017;127(11):4031–41. https://doi.org/10.1172/JCI93396.

  41. 41.

    Lande R, Botti E, Jandus C, Dojcinovic D, Fanelli G, Conrad C, et al. The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis. Nat Commun. 2014;5:5621. https://doi.org/10.1038/ncomms6621.

  42. 42.

    Cheung KL, Jarrett R, Subramaniam S, Salimi M, Gutowska-Owsiak D, Chen YL, et al. Psoriatic T cells recognize neolipid antigens generated by mast cell phospholipase delivered by exosomes and presented by CD1a. J Exp Med. 2016;213(11):2399–412. https://doi.org/10.1084/jem.20160258.

  43. 43.

    Arakawa A, Siewert K, Stohr J, Besgen P, Kim SM, Ruhl G, et al. Melanocyte antigen triggers autoimmunity in human psoriasis. J Exp Med. 2015;212(13):2203–12. https://doi.org/10.1084/jem.20151093.

  44. 44.

    Gallais Sérézal I, Classon C, Cheuk S, Barrientos-Somarribas M, Wadman E, Martini E, et al. Resident T cells in resolved psoriasis steer tissue responses that stratify clinical outcome. J Invest Dermatol. 2018;138(8):1754–63. https://doi.org/10.1016/j.jid.2018.02.030.

  45. 45.

    Vo S, Watanabe R, Koguchi-Yoshioka H, Matsumura Y, Ishitsuka Y, Nakamura Y, et al. CD8 resident memory T cells with IL-17A-producing potential are accumulated in disease-naive non-lesional sites of psoriasis possibly in correlation with disease duration. Br J Dermatol. 2019. https://doi.org/10.1111/bjd.17748.

  46. 46.

    Gallais Sérézal I, Hoffer E, Ignatov B, Martini E, Zitti B, Ehrstrom M, et al. A skewed pool of resident T cells triggers psoriasis-associated tissue responses in never-lesional skin from patients with psoriasis. J Allergy Clin Immunol. 2019;143(4):1444–54. https://doi.org/10.1016/j.jaci.2018.08.048.

  47. 47.

    Raimondo A, Lembo S, Di Caprio R, Donnarumma G, Monfrecola G, Balato N, et al. Psoriatic cutaneous inflammation promotes human monocyte differentiation into active osteoclasts, facilitating bone damage. Eur J Immunol. 2017;47(6):1062–74. https://doi.org/10.1002/eji.201646774.

  48. 48.

    Riding RL, Harris JE. The role of memory CD8(+) T cells in vitiligo. J Immunol. 2019;203(1):11–9. https://doi.org/10.4049/jimmunol.1900027.

  49. 49.

    Harris JE, Harris TH, Weninger W, Wherry EJ, Hunter CA, Turka LA. A mouse model of vitiligo with focused epidermal depigmentation requires IFN-gamma for autoreactive CD8(+) T-cell accumulation in the skin. J Invest Dermatol. 2012;132(7):1869–76. https://doi.org/10.1038/jid.2011.463.

  50. 50.

    Yang L, Wei Y, Sun Y, Shi W, Yang J, Zhu L, et al. Interferon-gamma inhibits melanogenesis and induces apoptosis in melanocytes: a pivotal role of CD8+ cytotoxic T lymphocytes in vitiligo. Acta Derm Venereol. 2015;95(6):664–70. https://doi.org/10.2340/00015555-2080.

  51. 51.

    Boniface K, Seneschal J. Vitiligo as a skin memory disease: the need for early intervention with immunomodulating agents and a maintenance therapy to target resident memory T cells. Exp Dermatol. 2019. https://doi.org/10.1111/exd.13879.

  52. 52.

    Richmond JM, Strassner JP, Rashighi M, Agarwal P, Garg M, Essien KI, et al. Resident memory and recirculating memory T cells cooperate to maintain disease in a mouse model of vitiligo. J Invest Dermatol. 2019;139(4):769–78. https://doi.org/10.1016/j.jid.2018.10.032.

  53. 53.

    Boniface K, Jacquemin C, Darrigade AS, Dessarthe B, Martins C, Boukhedouni N, et al. Vitiligo skin is imprinted with resident memory CD8 T cells expressing CXCR3. J Invest Dermatol. 2018;138(2):355–64. https://doi.org/10.1016/j.jid.2017.08.038.

  54. 54.

    Rashighi M, Agarwal P, Richmond JM, Harris TH, Dresser K, Su MW, et al. CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo. Sci Transl Med. 2014;6(223):223ra23. https://doi.org/10.1126/scitranslmed.3007811.

  55. 55.

    Richmond JM, Strassner JP, Zapata L Jr, Garg M, Riding RL, Refat MA, et al. Antibody blockade of IL-15 signaling has the potential to durably reverse vitiligo. Sci Transl Med. 2018. https://doi.org/10.1126/scitranslmed.aam7710.

  56. 56.

    Brunner PM, Emerson RO, Tipton C, Garcet S, Khattri S, Coats I, et al. Nonlesional atopic dermatitis skin shares similar T-cell clones with lesional tissues. Allergy. 2017;72(12):2017–25. https://doi.org/10.1111/all.13223.

  57. 57.

    Kim SPC, Shin J, Noh J, Kim H, Kim J, et al. 049 Multicytokine-producing tissue resident memory (TRM) cells in atopic dermatitis patient. J Investig Dermatol. 2016;136(5):S9.

  58. 58.

    Kim SKJ, Park C, Kupper T, Lee K. 22 Distinct transcriptome signature of skin-resident memory T cells and migratory memory T cells in atopic dermatitis. J Investig Dermatol. 2018;138(5):S4.

  59. 59.

    Gamradt P, Laoubi L, Nosbaum A, Mutez V, Lenief V, Grande S, et al. Inhibitory checkpoint receptors control CD8(+) resident memory T cells to prevent skin allergy. J Allergy Clin Immunol. 2019. https://doi.org/10.1016/j.jaci.2018.11.048.

  60. 60.

    As OG, Jee MH, Funch AB, Alhede M, Mraz V, Weber JF, et al. Pathogenic CD8(+) epidermis-resident memory T cells displace dendritic epidermal T cells in allergic dermatitis. J Invest Dermatol. 2019. https://doi.org/10.1016/j.jid.2019.07.722.

  61. 61.

    Ganesan AP, Clarke J, Wood O, Garrido-Martin EM, Chee SJ, Mellows T, et al. Tissue-resident memory features are linked to the magnitude of cytotoxic T cell responses in human lung cancer. Nat Immunol. 2017;18(8):940–50. https://doi.org/10.1038/ni.3775.

  62. 62.

    Lim CJ, Lee YH, Pan L, Lai L, Chua C, Wasser M, et al. Multidimensional analyses reveal distinct immune microenvironment in hepatitis B virus-related hepatocellular carcinoma. Gut. 2019;68(5):916–27. https://doi.org/10.1136/gutjnl-2018-316510.

  63. 63.

    Wang ZQ, Milne K, Derocher H, Webb JR, Nelson BH, Watson PH. CD103 and intratumoral immune response in breast cancer. Clin Cancer Res. 2016;22(24):6290–7. https://doi.org/10.1158/1078-0432.CCR-16-0732.

  64. 64.

    Edwards J, Wilmott JS, Madore J, Gide TN, Quek C, Tasker A, et al. CD103(+) tumor-resident CD8(+) t cells are associated with improved survival in immunotherapy-naive melanoma patients and expand significantly during anti-PD-1 treatment. Clin Cancer Res. 2018;24(13):3036–45. https://doi.org/10.1158/1078-0432.CCR-17-2257.

  65. 65.

    Murray T, Fuertes Marraco SA, Baumgaertner P, Bordry N, Cagnon L, Donda A, et al. Very late antigen-1 marks functional tumor-resident CD8 T cells and correlates with survival of melanoma patients. Front Immunol. 2016;7:573. https://doi.org/10.3389/fimmu.2016.00573.

  66. 66.

    Malik BT, Byrne KT, Vella JL, Zhang P, Shabaneh TB, Steinberg SM, et al. Resident memory T cells in the skin mediate durable immunity to melanoma. Sci Immunol. 2017. https://doi.org/10.1126/sciimmunol.aam6346.

  67. 67.

    Enamorado M, Iborra S, Priego E, Cueto FJ, Quintana JA, Martinez-Cano S, et al. Enhanced anti-tumour immunity requires the interplay between resident and circulating memory CD8(+) T cells. Nat Commun. 2017;8:16073. https://doi.org/10.1038/ncomms16073.

  68. 68.

    Park SL, Buzzai A, Rautela J, Hor JL, Hochheiser K, Effern M, et al. Tissue-resident memory CD8(+) T cells promote melanoma-immune equilibrium in skin. Nature. 2019;565(7739):366–71. https://doi.org/10.1038/s41586-018-0812-9.

  69. 69.

    Rosato PC, Wijeyesinghe S, Stolley JM, Nelson CE, Davis RL, Manlove LS, et al. Virus-specific memory T cells populate tumors and can be repurposed for tumor immunotherapy. Nat Commun. 2019;10(1):567. https://doi.org/10.1038/s41467-019-08534-1.

  70. 70.

    Boddupalli CS, Bar N, Kadaveru K, Krauthammer M, Pornputtapong N, Mai Z, et al. Interlesional diversity of T cell receptors in melanoma with immune checkpoints enriched in tissue-resident memory T cells. JCI Insight. 2016;1(21):e88955. https://doi.org/10.1172/jci.insight.88955.

  71. 71.

    Menares E, Galvez-Cancino F, Caceres-Morgado P, Ghorani E, Lopez E, Diaz X, et al. Tissue-resident memory CD8(+) T cells amplify anti-tumor immunity by triggering antigen spreading through dendritic cells. Nat Commun. 2019;10(1):4401. https://doi.org/10.1038/s41467-019-12319-x.

  72. 72.

    Gauthier L, Corgnac S, Boutet M, Gros G, Validire P, Bismuth G, et al. Paxillin binding to the cytoplasmic domain of CD103 promotes cell adhesion and effector functions for CD8(+) resident memory T cells in tumors. Cancer Res. 2017;77(24):7072–82. https://doi.org/10.1158/0008-5472.CAN-17-1487.

  73. 73.

    Zhu J, Peng T, Johnston C, Phasouk K, Kask AS, Klock A, et al. Immune surveillance by CD8alphaalpha+ skin-resident T cells in human herpes virus infection. Nature. 2013;497(7450):494–7. https://doi.org/10.1038/nature12110.

  74. 74.

    Jiang X, Clark RA, Liu L, Wagers AJ, Fuhlbrigge RC, Kupper TS. Skin infection generates non-migratory memory CD8+ T(RM) cells providing global skin immunity. Nature. 2012;483(7388):227–31. https://doi.org/10.1038/nature10851.

  75. 75.

    Sacirbegovic F, Zhu J, Liu J, Rosenberger S, Shlomchik MJ, Shlomchik WD. Identifying tissue-resident memory T cells in graft-versus-host disease. Blood. 2016;128(22):4544. https://doi.org/10.1182/blood.V128.22.4544.4544.

  76. 76.

    Clark RA, Watanabe R, Teague JE, Schlapbach C, Tawa MC, Adams N, et al. Skin effector memory T cells do not recirculate and provide immune protection in alemtuzumab-treated CTCL patients. Sci Transl Med. 2012;4(117):117ra7. https://doi.org/10.1126/scitranslmed.3003008.

  77. 77.

    Campbell JJ, Clark RA, Watanabe R, Kupper TS. Sezary syndrome and mycosis fungoides arise from distinct T-cell subsets: a biologic rationale for their distinct clinical behaviors. Blood. 2010;116(5):767–71. https://doi.org/10.1182/blood-2009-11-251926.

  78. 78.

    Rosenberg AR, Tabacchi M, Ngo KH, Wallendorf M, Rosman IS, Cornelius LA, et al. Skin cancer precursor immunotherapy for squamous cell carcinoma prevention. JCI Insight. 2019. https://doi.org/10.1172/jci.insight.125476.

  79. 79.

    Chen L, Shen Z. Tissue-resident memory T cells and their biological characteristics in the recurrence of inflammatory skin disorders. Cell Mol Immunol. 2019. https://doi.org/10.1038/s41423-019-0291-4.

  80. 80.

    Patra V, Laoubi L, Nicolas JF, Vocanson M, Wolf P. A perspective on the interplay of ultraviolet-radiation, skin microbiome and skin resident memory TCRalphabeta+ cells. Front Med (Lausanne). 2018;5:166. https://doi.org/10.3389/fmed.2018.00166.

  81. 81.

    MacLeod AS, Rudolph R, Corriden R, Ye I, Garijo O, Havran WL. Skin-resident T cells sense ultraviolet radiation-induced injury and contribute to DNA repair. J Immunol. 2014;192(12):5695–702. https://doi.org/10.4049/jimmunol.1303297.

  82. 82.

    Gebhardt T, Palendira U, Tscharke DC, Bedoui S. Tissue-resident memory T cells in tissue homeostasis, persistent infection, and cancer surveillance. Immunol Rev. 2018;283(1):54–76. https://doi.org/10.1111/imr.12650.

  83. 83.

    Shin H, Iwasaki A. A vaccine strategy that protects against genital herpes by establishing local memory T cells. Nature. 2012;491(7424):463–7. https://doi.org/10.1038/nature11522.

  84. 84.

    Fernandez-Ruiz D, Ng WY, Holz LE, Ma JZ, Zaid A, Wong YC, et al. Liver-resident memory CD8(+) T cells form a front-line defense against malaria liver-stage infection. Immunity. 2016;45(4):889–902. https://doi.org/10.1016/j.immuni.2016.08.011.

  85. 85.

    Willemsen M, Linkute R, Luiten RM, Matos TR. Skin-resident memory T cells as a potential new therapeutic target in vitiligo and melanoma. Pigment Cell Melanoma Res. 2019;32(5):612–22. https://doi.org/10.1111/pcmr.12803.

  86. 86.

    Sun H, Sun C, Xiao W, Sun R. Tissue-resident lymphocytes: from adaptive to innate immunity. Cell Mol Immunol. 2019;16(3):205–15. https://doi.org/10.1038/s41423-018-0192-y.

  87. 87.

    Pan Y, Tian T, Park CO, Lofftus SY, Mei S, Liu X, et al. Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism. Nature. 2017;543(7644):252–6. https://doi.org/10.1038/nature21379.

  88. 88.

    Pan Y, Kupper TS. Metabolic reprogramming and longevity of tissue-resident memory T cells. Front Immunol. 2018;9:1347. https://doi.org/10.3389/fimmu.2018.01347.

  89. 89.

    Steinbach K, Vincenti I, Merkler D. Resident-memory T cells in tissue-restricted immune responses: for better or worse? Front Immunol. 2018;9:2827. https://doi.org/10.3389/fimmu.2018.02827.

Download references



Author information

Correspondence to Ossama Abbas.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Responsible Editor: John Di Battista.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Khalil, S., Bardawil, T., Kurban, M. et al. Tissue-resident memory T cells in the skin. Inflamm. Res. 69, 245–254 (2020). https://doi.org/10.1007/s00011-020-01320-6

Download citation


  • Tissue-resident T cells
  • Psoriasis
  • Melanoma
  • Fixed drug eruption
  • Dermatitis