Barros-Martins, J. | bioRxiv Science

bioRxiv2024

Integrative deep immune profiling of the elderly reveals systems-level signatures of aging, sex, smoking, and clinical traits

Elderly individuals have higher disease susceptibility and lower vaccine responsiveness, highlighting the need to better comprehend the aging immune system and its clinical associations. Here we conducted a deep immune profiling study of 550 elderly individuals (61-94 years) and 100 young adults (22-38 years). Utilizing high-dimensional spectral flow cytometry to identify 97 immune cell populations and 48-plex cytokine profiling, we detailed intricate age-and sex-related changes in the elderly immune system at an unprecedented depth. Synthesizing information from clinical, laboratory, and immunological data through an integrative multi-block analysis, we reveal overarching systems-level signatures of aging, such as increased concentrations of specific cytokines and frequencies of defined innate and adaptive immune cell subpopulations. Extending this approach, we identified unique immune signatures of smoking, obesity, and several diseases including osteoporosis, heart failure and gout. Our systems biology approach enables to uncover new relationships between clinical characteristics and immunological traits.

immunology↗

bioRxiv2023

Adult thymus-derived cMaf+ RORγt+ γδ T cells lack Scart2 chromatin accessibility and do not reach periphery

T cell receptor (TCR) V{gamma}4+ expressing {gamma}{delta} T cells can be divided into IFN-{gamma} and IL-17-producing effector T cell subsets. A bias towards {gamma}{delta}17 effector fate decisions is observed during early ontogeny. In contrast, the existence of V{gamma}4+ {gamma}{delta}17 cells derived from adult thymus is still controversial. In the present work, we used a mouse model where T cells are exclusive generated within an adult thymus. Additionally, we employed single-cell chromatin state analysis from thymocytes of normal mice. A small, but considerable population of immature Cd24+ Gzma+ V{gamma}4 cells was found that exhibit molecular programs of {gamma}{delta}17 cells. These adult thymus-derived immature Cd24a+ cMaf+ V{gamma}4 cells secrete small amounts of IL-17A and IL-17F. Interestingly, do not reach the periphery under steady-state conditions. Furthermore, de novo generated {gamma}{delta}17-like cells from adult thymus lack transcriptional activity of the Scart2 encoding gene, suggesting that Scart2 is a distinct trait of fetal {gamma}{delta} T cell precursors. Together, this study provides valuable insights into developmental traits of V{gamma}4 cells during adulthood and raises the question on signals suppressing the full maturation and/or thymic export of {gamma}{delta}17-like cells within the adult thymus. HighlightsO_LITranscriptional and epigenetic profiling identifies developmental plasticity of Gzma+ Cd24a+ V{gamma}4 cells in adult thymus. C_LIO_LIThymic c-Maf+ and ROR{gamma}t+ V{gamma}4 T cells can be generated during adulthood, but do not reach the periphery under steady-state conditions. C_LIO_LIInnate CD44highCD45RBneg {gamma}{delta}17 cells are completely absent upon induction of T cell development during adulthood. C_LIO_LIScart2 expression might be a key molecule to track developmental traits of fetal-derived {gamma}{delta}17 cell precursors. C_LI

immunology↗