Skin Infiltration of Pathogenic Migratory and Resident T Cells Is Decreased by Secukinumab Treatment in Psoriasis

Fujiyama, Toshiharu; Umayahara, Takatsune; Kurihara, Kenzo; Shimauchi, Takatoshi; Ito, Taisuke; Aoshima, Masahiro; Otobe, Emiko; Hashizume, Hideo; Yanagimoto, Hiroaki; Tokura, Y.

doi:10.1016/j.jid.2020.02.024

Cited by 16 publications

(17 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our clinical study in psoriasis patients, the cells with T RM markers were increased in the active skin lesion and decreased after the systemic treatment with anti-IL-17A mAb, although they were relatively resistance to the treatment compared to the non-T RM cells (142). In addition, T cells bearing T RM markers in the active lesion were capable of producing pathogenic cytokines, such as IL-17A, and were possibly related to the unfavorable disease course (70).…”

Section: Discussionmentioning

confidence: 66%

“…When CD103 + , CD103 -, CD69 + , and CD69 -T cells were isolated and expanded ex vivo with anti-CD3/CD28 Ab and IL-2 (140)(141)(142), the positive and negative expression of CD103 was unchanged (70). However, CD69 expression can be changed bidirectionally by cultivation, suggesting the unsteady, fluctuated expression of CD69.…”

Section: Skin T Rm Cells In Psoriasismentioning

confidence: 99%

“…However, CD69 expression can be changed bidirectionally by cultivation, suggesting the unsteady, fluctuated expression of CD69. By using skin-derived, ex vivo expanded T cells (140)(141)(142), we conducted to characterize the cytokine profile of CD103 + skin T RM cells, especially, epidermal CD8 + CD103 + T RM cells (39,74). In T cell samples expanded from psoriasis lesional skin, a part of CD8 + T cells co-expressed CD103, and this CD8 + CD103 + T cells are considered to be epidermal T RM cells.…”

Section: Skin T Rm Cells In Psoriasismentioning

confidence: 99%

“…In the epidermis, both CD8 + CD103 + and CD4 + CD103 + T RM are present and have potent effector functions (14), although the former CD8 + population is present at a higher frequency in the normal and psoriatic lesional skin (70,138,142). Skin T RM in the dermis are CD4 + CD69 + CD103 -.…”

Section: Skin T Rm Cells In Cutaneous Lymphomasmentioning

confidence: 99%

See 3 more Smart Citations

Pathophysiology of Skin Resident Memory T Cells

et al. 2021

Self Cite

View full text Add to dashboard Cite

Tissue resident memory T (TRM) cells reside in peripheral, non-lymphoid tissues such as the skin, where they act as alarm-sensor cells or cytotoxic cells. Physiologically, skin TRM cells persist for a long term and can be reactivated upon reinfection with the same antigen, thus serving as peripheral sentinels in the immune surveillance network. CD8+CD69+CD103+ TRM cells are the well-characterized subtype that develops in the epidermis. The local mediators such as interleukin (IL)-15 and transforming growth factor (TGF)-β are required for the formation of long-lived TRM cell population in skin. Skin TRM cells engage virus-infected cells, proliferate in situ in response to local antigens and do not migrate out of the epidermis. Secondary TRM cell populations are derived from pre-existing TRM cells and newly recruited TRM precursors from the circulation. In addition to microbial pathogens, topical application of chemical allergen to skin causes delayed-type hypersensitivity and amplifies the number of antigen-specific CD8+ TRM cells at challenged site. Skin TRM cells are also involved in the pathological conditions, including vitiligo, psoriasis, fixed drug eruption and cutaneous T-cell lymphoma (CTCL). The functions of these TRM cells seem to be different, depending on each pathology. Psoriasis plaques are seen in a recurrent manner especially at the originally affected sites. Upon stimulation of the skin of psoriasis patients, the CD8+CD103+CD49a- TRM cells in the epidermis seem to be reactivated and initiate IL-17A production. Meanwhile, autoreactive CD8+CD103+CD49a+ TRM cells secreting interferon-γ are present in lesional vitiligo skin. Fixed drug eruption is another disease where skin TRM cells evoke its characteristic clinical appearance upon administration of a causative drug. Intraepidermal CD8+ TRM cells with an effector-memory phenotype resident in the skin lesions of fixed drug eruption play a major contributing role in the development of localized tissue damage. CTCL develops primarily in the skin by a clonal expansion of a transformed TRM cells. CD8+ CTCL with the pagetoid epidermotropic histology is considered to originate from epidermal CD8+ TRM cells. This review will discuss the current understanding of skin TRM biology and their contribution to skin homeostasis and diseases.

show abstract

Section: Discussionmentioning

confidence: 66%

Section: Skin T Rm Cells In Psoriasismentioning

confidence: 99%

Section: Skin T Rm Cells In Psoriasismentioning

confidence: 99%

Section: Skin T Rm Cells In Cutaneous Lymphomasmentioning

confidence: 99%

See 2 more Smart Citations

Pathophysiology of Skin Resident Memory T Cells

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our recent study demonstrates that secukinumab suppresses skin infiltration of IL-17A-producing cells, including T-helper 17 cells and resident memory T cells. 2,3 Cholecystokinin (CCK) is widely distributed in the digestive organs and the central nervous system, and functions as a peptide hormone through its specific receptors, CCKA receptor (CCKAR) and CCKB receptor. 4,5 We have demonstrated that CCK is produced by epidermal keratinocytes in the skin and plays a suppressive role in psoriasis development and peripheral pruritus.…”

mentioning

confidence: 99%

Secukinumab promotes engagement of cholecystokinin and its receptor in epidermal keratinocytes of psoriasis patients

Funakoshi

Fujiyama

Tatsuno

et al. 2020

The Journal of Dermatology

Self Cite

View full text Add to dashboard Cite

show abstract

The Immunology of Psoriasis—Current Concepts in Pathogenesis

Sieminska,

Pieniawska,

Grzywa

2024

Clinic Rev Allerg Immunol

View full text Add to dashboard Cite

Psoriasis is one of the most common inflammatory skin diseases with a chronic, relapsing-remitting course. The last decades of intense research uncovered a pathological network of interactions between immune cells and other types of cells in the pathogenesis of psoriasis. Emerging evidence indicates that dendritic cells, TH17 cells, and keratinocytes constitute a pathogenic triad in psoriasis. Dendritic cells produce TNF-α and IL-23 to promote T cell differentiation toward TH17 cells that produce key psoriatic cytokines IL-17, IFN-γ, and IL-22. Their activity results in skin inflammation and activation and hyperproliferation of keratinocytes. In addition, other cells and signaling pathways are implicated in the pathogenesis of psoriasis, including TH9 cells, TH22 cells, CD8+ cytotoxic cells, neutrophils, γδ T cells, and cytokines and chemokines secreted by them. New insights from high-throughput analysis of lesional skin identified novel signaling pathways and cell populations involved in the pathogenesis. These studies not only expanded our knowledge about the mechanisms of immune response and the pathogenesis of psoriasis but also resulted in a revolution in the clinical management of patients with psoriasis. Thus, understanding the mechanisms of immune response in psoriatic inflammation is crucial for further studies, the development of novel therapeutic strategies, and the clinical management of psoriasis patients. The aim of the review was to comprehensively present the dysregulation of immune response in psoriasis with an emphasis on recent findings. Here, we described the role of immune cells, including T cells, B cells, dendritic cells, neutrophils, monocytes, mast cells, and innate lymphoid cells (ILCs), as well as non-immune cells, including keratinocytes, fibroblasts, endothelial cells, and platelets in the initiation, development, and progression of psoriasis.

show abstract

Skin Infiltration of Pathogenic Migratory and Resident T Cells Is Decreased by Secukinumab Treatment in Psoriasis

Cited by 16 publications

References 11 publications

Pathophysiology of Skin Resident Memory T Cells

Pathophysiology of Skin Resident Memory T Cells

Secukinumab promotes engagement of cholecystokinin and its receptor in epidermal keratinocytes of psoriasis patients

The Immunology of Psoriasis—Current Concepts in Pathogenesis

Contact Info

Product

Resources

About