The menstrual cycle regulates migratory CD4 T-cell surveillance in the female reproductive tract via CCR5 signaling
Year: 2023
Type: article
Abstract: Despite their importance for immunity against sexually transmitted infections, the composition of female reproductive tract (FRT) memory T-cell populations in response to changes within the local tissue environment under the regulation of the menstrual cycle remains poorly defined. Here, we show that in humans and pig-tailed macaques, the cycle determines distinct clusters of differentiation 4 T-cell surveillance behaviors by subsets corresponding to migratory memory (T MM ) and resident memory T cells. T MM displays tissue-itinerant trafficking characteristics, restricted distribution within the FRT microenvironment, and distinct effector responses to infection. Gene pathway analysis by RNA sequencing identified T MM -specific enrichment of genes involved in hormonal regulation and inflammatory responses. FRT T-cell subset fluctuations were discovered that synchronized to cycle-driven CCR5 signaling. Notably, oral administration of a CCR5 antagonist drug blocked T MM trafficking. Taken together, 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 immune surveillance at the site of STI pathogen exposure.
Source: Mucosal Immunology
Authors: M. Elliott Williams, Felica P. Hardnett, Anandi N. Sheth, Alexander N. Wein, Zheng-Rong Tiger Li, Jessica Radzio-Basu, Chuong Dinh, Lisa B. Haddad, Elizabeth M.B. Collins, Igho Ofotokun, Rustom Antia, Christopher D. Scharer, J. Gerardo Garcia-Lerma, Jacob E. Kohlmeier, Alison Swaims-Kohlmeier
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,800
Funders: Emory University, National Institutes of Health, Centers for Disease Control and Prevention, School of Medicine, Emory University, Center for AIDS Research, University of Washington, Yerkes National Primate Research Center, Emory University, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Atlanta Clinical and Translational Science Institute (UL1), G2675028044, G2764422858, Impact of progestin contraception on risk of HIV acquisition and transmission, G3879473163, G4160209598, Atlanta Clinical and Translational Science Institute (ACTSI) Renewal, Atlanta Clinical and Translational Science Institute (ACTSI) Renewal, G6113675784, G6699147628, G7094225672, Multiscale modeling of influenza vaccination strategies for optimal T cell immunity, G7798477230, Characterization and modulation of mucosal immunity for HIV prevention in women, Center for AIDS Research at Emory University, Georgia Clinical & Translational Science Alliance (Georgia CTSA), Cellular and molecular programming of lung resident T cell memory, Emory National Primate Research Center
OpenAlex ID: W4387826486