A role for the CCR5–CCL5 interaction in the preferential migration of HSV-2-specific effector cells to the vaginal mucosa upon nasal immunization

Joo, Sunyi; Suwanto, Aldina; Sato, Ayuko; Nakahashi-Ouchida, Rika; Mori, Hiromi; Uchida, Yohei; Sato, Shintaro; Kurashima, Yosuke; Yuki, Yoshikazu; Fujihashi, Kohtaro; Kawaguchi, Yasushi; Kiyono, Hiroshi

doi:10.1038/s41385-019-0203-z

Cited by 7 publications

(6 citation statements)

References 51 publications

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“…CCR5 chemokines are constitutively produced from FRT epithelial cells, local innate immune cells and potentially by underlying stromal cells ( 8, 14, 22, 58, 59 ). Furthermore, artificially modifying FRT barrier integrity through high dose progestin-based contraception such as injectable depot medroxyprogesterone acetate (DMPA) leads to an increase in FRT CCR5-expressing CD4 T cells ( 60, 61 ), suggesting that progesterone signaling pathways can modulate CD4 T cell trafficking to the FRT through changes in the vaginal epithelium or local chemokine production.…”

Section: Discussionmentioning

confidence: 99%

“…Similar to other mucosal tissues, CD4 T cell migration into the FRT is regulated by specific chemokine receptors and integrins ( 10, 11 ). In response to an infection, CCR5, CXCR3, and α4β1 have been identified as important for antigen-specific T cell trafficking to both the upper and lower FRT ( 12–14 ). Whereas in the absence of infection (homeostatic conditions) it is thought that very little T cell trafficking into the FRT occurs, and local recall responses depend upon tissue-anchored resident memory T cells ( 15, 16 ).…”

Section: Introductionmentioning

confidence: 99%

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Memory CD4 T cell subset organization in the female reproductive tract is regulated via the menstrual cycle through CCR5 signaling

Swaims-Kohlmeier

Wein

Hardnett³

et al. 2022

Preprint

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Despite their importance for immunity against sexually transmitted infections (STIs), the composition of the female reproductive tract (FRT) memory CD4 T cell population in response to changes in the local tissue environment during the menstrual cycle remains poorly defined. Here we show that across humans, non-human primates (NHP), and mice, FRT CD4 T cells comprise distinct subsets corresponding to migratory memory (TMM) and resident memory (TRM) cells. TMM display tissue-itinerant trafficking characteristics, restricted FRT tissue distribution, with distinct transcriptional properties and effector responses to infection. CD4 T cell subset fluctuations synchronized with cycle-driven proinflammatory changes within the local tissue environment and oral administration of a CCR5 antagonist inhibited cycle phase-specific migratory T cell surveillance. This study provides novel insights into the dynamic nature of FRT memory CD4 T cells and identifies the menstrual cycle as a key regulator of memory T cell defense at the site of STI exposure.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Memory CD4 T cell subset organization in the female reproductive tract is regulated via the menstrual cycle through CCR5 signaling

Swaims-Kohlmeier

Wein

Hardnett³

et al. 2022

Preprint

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“…4d, e). Cells from C2 were CD8 + effector cells (Tef8), as they expressed genes related to effector T cell functions (CCL5, GZMA, PRF1, GNLY, and IFNG) [40][41][42] and the AP1 family (JUN) (Fig. 4d, e) 43 .…”

Section: Carp T Cells Promote Carmz T Cell To Differentiate To Centra...mentioning

confidence: 99%

Co-expression of a PD-L1-specific chimeric switch receptor augments the efficacy and persistence of CAR T cells via the CD70-CD27 axis

et al. 2022

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Co-expression of chimeric switch receptors (CSRs) specific for PD-L1 improves the antitumor effects of chimeric antigen receptor (CAR) T cells. However, the effects of trans-recognition between CSRs and PD-L1 expressed by activated CAR T cells remain unclear. Here, we design a CSR specific for PD-L1 (CARP), containing the transmembrane and cytoplasmic signaling domains of CD28 but not the CD3 ζ chain. We show that CARP T cells enhance the antitumor activity of anti-mesothelin CAR (CARMz) T cells in vitro and in vivo. In addition, confocal microscopy indicates that PD-L1 molecules on CARMz T cells accumulate at cell-cell contacts with CARP T cells. Using single-cell RNA-sequencing analysis, we reveal that CARP T cells promote CARMz T cells differentiation into central memory-like T cells, upregulate genes related to Th1 cells, and downregulate Th2-associated cytokines through the CD70-CD27 axis. Moreover, these effects are not restricted to PD-L1, as CAR19 T cells expressing anti-CD19 CSR exhibit similar effects on anti-PSCA CAR T cells with truncated CD19 expression. These findings suggest that target trans-recognition by CSRs on CAR T cells may improve the efficacy and persistence of CAR T cells via the CD70-CD27 axis.

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“…Currently, it is known that the influence of CCR5 and CCR5D32 goes beyond protection against HIV infection and is much broader than previously believed, influencing the susceptibility and outcome of different conditions, such as other different viral, bacterial, and parasitic diseases (40,92), as well as non-infectious inflammatory conditions (93)(94)(95)(96). This occurs because the lack of CCR5 expression, in humans naturally due to CCR5D32, interferes with multiple aspects of inflammatory responses, including expression of immune system genes, levels of inflammatory markers, and activity of immune cells (97)(98)(99)(100)(101)(102)(103). On the other hand, now looking at the undesirable aspects of CCR5D32, this genetic variant increases the risk of serious complications caused by the West Nile virus and Tick-borne encephalitis virus (104)(105)(106)(107)(108)(109).…”

Section: Pivotal Information Regarding the Ccr5d32 Variantmentioning

confidence: 99%

CCR5Δ32 in Brazil: Impacts of a European Genetic Variant on a Highly Admixed Population

Kulmann-Leal

Ellwanger

2021

Front. Immunol.

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The genetic background of Brazilians encompasses Amerindian, African, and European components as a result of the colonization of an already Amerindian inhabited region by Europeans, associated to a massive influx of Africans. Other migratory flows introduced into the Brazilian population genetic components from Asia and the Middle East. Currently, Brazil has a highly admixed population and, therefore, the study of genetic factors in the context of health or disease in Brazil is a challenging and remarkably interesting subject. This phenomenon is exemplified by the genetic variant CCR5Δ32, a 32 base-pair deletion in the CCR5 gene. CCR5Δ32 originated in Europe, but the time of origin as well as the selective pressures that allowed the maintenance of this variant and the establishment of its current frequencies in the different human populations is still a field of debates. Due to its origin, the CCR5Δ32 allele frequency is high in European-derived populations (~10%) and low in Asian and African native human populations. In Brazil, the CCR5Δ32 allele frequency is intermediate (4-6%) and varies on the Brazilian States, depending on the migratory history of each region. CCR5 is a protein that regulates the activity of several immune cells, also acting as the main HIV-1 co-receptor. The CCR5 expression is influenced by CCR5Δ32 genotypes. No CCR5 expression is observed in CCR5Δ32 homozygous individuals. Thus, the CCR5Δ32 has particular effects on different diseases. At the population level, the effect that CCR5Δ32 has on European populations may be different than that observed in highly admixed populations. Besides less evident due to its low frequency in admixed groups, the effect of the CCR5Δ32 variant may be affected by other genetic traits. Understanding the effects of CCR5Δ32 on Brazilians is essential to predict the potential use of pharmacological CCR5 modulators in Brazil. Therefore, this study reviews the impacts of the CCR5Δ32 on the Brazilian population, considering infectious diseases, inflammatory conditions, and cancer. Finally, this article provides a general discussion concerning the impacts of a European-derived variant, the CCR5Δ32, on a highly admixed population.

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A role for the CCR5–CCL5 interaction in the preferential migration of HSV-2-specific effector cells to the vaginal mucosa upon nasal immunization

Cited by 7 publications

References 51 publications

Memory CD4 T cell subset organization in the female reproductive tract is regulated via the menstrual cycle through CCR5 signaling

Memory CD4 T cell subset organization in the female reproductive tract is regulated via the menstrual cycle through CCR5 signaling

Co-expression of a PD-L1-specific chimeric switch receptor augments the efficacy and persistence of CAR T cells via the CD70-CD27 axis

CCR5Δ32 in Brazil: Impacts of a European Genetic Variant on a Highly Admixed Population

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