IL-15 enhances CCR5-mediated migration of memory CD8+ T cells by upregulating CCR5 expression in the absence of TCR stimulation

Seo, In-Ho; Eun, Hyuk Soo; Kim, Ja Kyung; Lee, Hoyoung; Jeong, Seongju; Choi, Seong Jin; Lee, Byung Seok; Kim, Seok Hyun; Rou, Woo Sun; Lee, Dong Hoon; Kim, Won; Park, Su–Hyung; Shin, Eui Cheol

doi:10.1016/j.celrep.2021.109438

Cited by 19 publications

(29 citation statements)

References 23 publications

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“…We found that CD8 + T cells express CCR5 preferentially at the lesions compared to the dLN. Consistent with our observation, CCR5 is mainly expressed by effector and memory CD8 + T cells [39],[13,37,38,41], while naïve CD8 + T cells express CCR5 in a transient manner in the draining lymph node [54,55]. Also, our results show that Rag1 -/- mice reconstituted with CD8 + T cells have an enrichment of CCR5 and its ligands compared to Rag1 -/- mice reconstituted with CD8 + and CD4 + T cells, suggesting that this chemotactic pathway is a feature of increased pathology derived from cytolytic CD8 + T cells activity.…”

Section: Discussionsupporting

confidence: 92%

CCR5 promotes the migration of CD8⁺T cells to the leishmanial lesions

Sacramento,

Amorim,

Lombana

et al. 2023

Preprint

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Cytolytic CD8+T cells mediate immunopathology in cutaneous leishmaniasis without controlling parasites. Here, we identify factors involved in CD8+T cell migration to the lesion that could be targeted to ameliorate disease severity. CCR5 was the most highly expressed chemokine receptor in patient lesions, and the high expression of CCL3 and CCL4, CCR5 ligands, was associated with delayed healing of lesions. To test the requirement for CCR5,Leishmania-infected Rag1-/-mice were reconstituted with CCR5-/-CD8+T cells. We found that these mice developed smaller lesions accompanied by a reduction in CD8+T cell numbers compared to controls. We confirmed these findings by showing that the inhibition of CCR5 with maraviroc, a selective inhibitor of CCR5, reduced lesion development without affecting the parasite burden. Together, these results reveal that CD8+T cells migrate to leishmanial lesions in a CCR5-dependent manner and that blocking CCR5 prevents CD8+T cell-mediated pathology.

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Section: Discussionsupporting

confidence: 92%

CCR5 promotes the migration of CD8⁺T cells to the leishmanial lesions

Sacramento,

Amorim,

Lombana

et al. 2023

Preprint

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“…reported that HAV-unrelated CD8 + T cells were activated by IL-15 and developed intrinsic cytotoxicity via NKG2D and NKp30 leading to liver injury ( 1 ). They also suggest that the migration of bystander-activated memory CD8 + T cells from the circulation to the liver is mediated by CCR5 ( 37 ).…”

Section: Bystander Activation Of Various T Cell Typesmentioning

confidence: 99%

Emerging role of bystander T cell activation in autoimmune diseases

Shim

Cho

Shin

et al. 2022

BMB Rep

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Autoimmune disease is known to be caused by unregulated selfantigen-specific T cells, causing tissue damage. Although antigen specificity is an important mechanism of the adaptive immune system, antigen non-related T cells have been found in the inflamed tissues in various conditions. Bystander T cell activation refers to the activation of T cells without antigen recognition. During an immune response to a pathogen, bystander activation of self-reactive T cells via inflammatory mediators such as cytokines can trigger autoimmune diseases. Other antigen-specific T cells can also be bystander-activated to induce innate immune response resulting in autoimmune disease pathogenesis along with self-antigen-specific T cells. In this review, we summarize previous studies investigating bystander activation of various T cell types (NKT, γδ T cells, MAIT cells, conventional CD4+ , and CD8 + T cells) and discuss the role of innate-like T cell response in autoimmune diseases. In addition, we also review previous findings of bystander T cell function in infection and cancer. A better understanding of bystander-activated T cells versus antigenstimulated T cells provides a novel insight to control autoimmune disease pathogenesis. [BMB Reports 2022; 55(2): 57-64]

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“…Additionally, CCR5 has been reported to be upregulated by IL-15, causing migration of bystander CD8 T cells to the infection site to mediate enhanced liver injury in acute hepatitis A (50).…”

Section: Discussionmentioning

confidence: 99%

“…CXCR3 ligands such as CXCL9 and CXCL10 also cause bystander T cell migration in the case of Lyme disease, causing inflammation in joints and arthritis ( 16 ). Additionally, CCR5 has been reported to be upregulated by IL-15, causing migration of bystander CD8 + T cells to the infection site to mediate enhanced liver injury in acute hepatitis A ( 50 ).…”

Section: Discussionmentioning

confidence: 99%