Blood to skin recirculation of CD4 + memory T cells associates with cutaneous and systemic manifestations of psoriatic disease

Diani, Marco; Galasso, Marco; Cozzi, Chiara; Sgambelluri, Francesco; Altomare, A.; Cigni, Clara; Frigerio, E.; Drago, Lorenzo; Volinia, Stefano; Granucci, Francesca; Altomare, G. F.; Reali, Eva

doi:10.1016/j.clim.2017.04.001

Cited by 25 publications

(32 citation statements)

References 34 publications

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“…Therefore, we used SPADE analysis to study the expression levels of mTOR, STAT5A/B, STAT3, JAK3, ERK1/2, NF-κB p65, and AKT1/2/3, which are key players in immune responses. Among these protein profiles, we found the elevated levels mTOR, STAT3, and JAK3 were mainly restrictedly to CD4 TEM cells, which play a vital role in PS (35). In the PS group, JAK3 levels were markedly higher in CD4 T cells, especially CD4 TEM cells, and Th2 cells and were higher than those in the HC group ( Figure 3C).…”

Section: Discussionmentioning

confidence: 88%

Lymphocyte mass cytometry identifies a CD3-CD4+ cells subset with a potential role in psoriasis

et al. 2019

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Section: Discussionmentioning

confidence: 88%

Lymphocyte mass cytometry identifies a CD3-CD4+ cells subset with a potential role in psoriasis

et al. 2019

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“…Along this line, in psoriatic patients both gene expression analysis and circulating T cell phenotype suggest recruitment of CXCR3 + and CCR5 + cells to the inflamed skin associated with upregulation of the skin expression of their ligand CXCL10 and CCL5 (19,24).…”

Section: Discussionmentioning

confidence: 96%

“…Samples were acquired using FACSAriaII (BD biosciences) flow cytometer (19,24) and analyzed with the FlowJo software (Tree Star, Ashland, OR). A representative gating strategy is shown in Supplemental Figure 3.…”

Section: T Cell Isolation and Facs Analysismentioning

confidence: 99%

CCR4+ Skin-Tropic Phenotype as a Feature of Central Memory CD8+ T Cells in Healthy Subjects and Psoriasis Patients

et al. 2020

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The chemokine receptor CCR4 has emerged as a skin-homing molecule important for the migration of T cells from the blood to the dermis. From our previous data on psoriasis patients, CCR4 + memory T cells emerged as a putative recirculating population between skin and blood. Here we focused our attention on the expression of CCR4 and skin-tropic molecules in the different stages of memory T cell differentiation. We analyzed the chemokine receptor profile in CD8 + and CD4 + CD45RA − CCR7 + (T CM) and CD45RA − CCR7 − (T EM) cells. Subpopulations were further divided on the basis of CD62L expression, and the distribution among the subsets of the skin-homing molecule CLA (Cutaneous Lymphocyte Antigen) was evaluated. The characterization was performed on peripheral blood mononuclear cells isolated from 21 healthy subjects and 24 psoriasis patients. The results indicate that (i) the skin-homing CCR4 marker is mainly expressed in T CM cells, (ii) CCR4 + T CM cells also express high level of CLA and that (iii) the more differentiated phenotype T EM expresses CXCR3 and CCR5 but lower level of CCR4 and CLA. This indicates that progressive stages of memory T cell differentiation have profoundly different chemokine receptor patterns, with CD8 + T CM displaying a marked skin-tropic phenotype CLA + CCR4 +. Differential skin-tropic phenotype between T CM and T EM cells was observed in both healthy subjects and psoriasis patients. However, patients showed an expanded circulating population of CD8 + T CM cells with phenotype CCR4 + CXCR3 + that could play a role in the pathophysiology of psoriasis and possibly in disease recurrence.

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“…In addition to cytokines, lipids available in the skin are essential to maintain TRM [10,17] Figure 2. The receptors and secretory activity of tissue resident memory (TRM) CD8+ [5,22] TRMs have been described in unchanged, healed skin in places of recurrent psoriasis, which indicates their role in the disease's local memory [28]. Recirculation of memory T cells between the skin and circulation is a newly recognized immunological mechanism that plays an important role in the initiation of psoriasiform response [3,29,30] (Figure 3).…”

Section: Tissue Resident Memory Cells In Psoriasismentioning

confidence: 99%

Immunological Memory of Psoriatic Lesions

Owczarczyk‐Saczonek

Krajewska–Włodarczyk

Kasprowicz-Furmańczyk

et al. 2020

IJMS

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The natural course of psoriasis is the appearance of new lesions in the place of previous ones, which disappeared after a successful therapy. Recent studies of psoriasis etiopathogenesis showed that after psoriatic plaques have disappeared, in healthy skin we can still find a trace of inflammation in the form of tissue resident memory cells (TRM). They are originally responsible for protection against viral and bacterial infections in non-lymphatic tissues. In psoriatic inflammation, they are characterized by heterogeneity depending on their origin. CD8+ T cells TRM are abundantly present in psoriatic epidermis, while CD4+ TRM preferentially populate the dermis. In psoriasis, epidermal CD8+ TRM cells express CLA, CCR6, CD103 and IL-23R antigen and produce IL-17A during ex vivo stimulation. However, CD4+ CD103+ TRM can also colonize the epidermis and produce IL-22 during stimulation. Besides T cells, Th22 and epidermal DCs proved that epidermal cells in healed skin were still present and functioning after several years of disease remission. It explains the clinical phenomenon of the tendency of psoriatic lesions to relapse in the same location and it allows to develop new therapeutic strategies in the future.

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Blood to skin recirculation of CD4 + memory T cells associates with cutaneous and systemic manifestations of psoriatic disease

Cited by 25 publications

References 34 publications

Lymphocyte mass cytometry identifies a CD3-CD4+ cells subset with a potential role in psoriasis

Lymphocyte mass cytometry identifies a CD3-CD4+ cells subset with a potential role in psoriasis

CCR4+ Skin-Tropic Phenotype as a Feature of Central Memory CD8+ T Cells in Healthy Subjects and Psoriasis Patients

Immunological Memory of Psoriatic Lesions

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