Skin-Resident Memory T Cells: Pathogenesis and Implication for the Treatment of Psoriasis

Abstract

Tissue-resident memory T cells (TRM) stay in the peripheral tissues for long periods of time, do not recirculate, and provide the first line of adaptive immune response in the residing tissues. Although TRM originate from circulating T cells, TRM are physiologically distinct from circulating T cells with the expression of tissue-residency markers, such as CD69 and CD103, and the characteristic profile of transcription factors. Besides defense against pathogens, the functional skew of skin TRM is indicated in chronic skin inflammatory diseases. In psoriasis, IL-17A-producing CD8+ TRM are regarded as one of the pathogenic populations in skin. Although no licensed drugs that directly and specifically inhibit the activity of skin TRM are available to date, psoriatic skin TRM are affected in the current treatments of psoriasis. Targeting skin TRM or using TRM as a potential index for disease severity can be an attractive strategy in psoriasis.

The Effect of the Long-Term Calcipotriol/Betamethasone Dipropionate Local Therapy on Tissue Resident Memory Cells Markers in Psoriatic Eruptions

“…To date, no registered drugs are available that directly and specifically inhibit activity of skin TRM; however, current treatments for psoriasis are known to affect TRM of skin with psoriasis [ 10 , 13 ]. There are still few studies available in the literature describing the effect of systemic therapy—biological drugs, systemic drugs and phototherapy—on TRM in the skin of patients.…”

“…CD8+ TRM in the skin of patients suffering from psoriasis express the IL23 receptor, and, therefore, are able to produce pro-inflammatory interleukin (IL)-17 and IL-22 in the psoriatic skin, even for many months after remission [ 4 , 9 ]. In psoriasis, CD8+ TRM-producing IL-17A are considered to be one of the pathogenic skin populations involved in the pathogenesis of the disease [ 10 ].…”

Current developments and perspectives in psoriasis

“…62,77,78 This includes more detailed elucidation of elements of adaptive immunity, for example, the function of regulatory T cells, resident memory T cells, or other T-cell subpopulations beyond Th17 cells. [79][80][81] It also includes identifying tipping points in immune cybernetic regulatory circuits that control disease progression in different directions. 3.…”

“…"Immunological memory" has been known for some time in psoriatic skin lesions. 93 But more recently, clinical and experimental evidence is accumulating that suggests a central role of both immunological regulation, for example the central role of so-called tissue resident memory cells, 80,81,93,94 and epithelial "memory functions", [82][83][84] in the initiation, course, and expression of psoriasis. Therefore, we think that especially in connection with the fundamental influence of the disease process (disease modification) the scientific research of such and additional mechanisms will increase.…”

Aktuelle Entwicklungen und Perspektiven bei Psoriasis

“…Das "immunologische Gedächtnis" ist bei psoriatischen Hautläsionen schon länger bekannt. 93 Aber in jüngerer Zeit verdichten sich klinische und experimentelle Evidenz, die eine zentrale Rolle sowohl immunologischer Regulationen, beispielsweise die zentrale Rolle sogenannter tissue resident memory cells, 80,81,93,94 als auch epithelialer "Gedächtnisfunktionen", [82][83][84] für Auslösung, Verlauf, und Ausprägung der Psoriasis nahelegen. Wir denken daher, dass gerade auch im Zusammenhang mit der grundsätzlichen Beeinflussung des Krankheitsprozesses (disease modification) die wissenschaftliche Erforschung derartiger und weiterer Mechanismen zunehmen wird.…”