TY  - JOUR
A1  - Schlecht, Anja
A1  - Thien, Adrian
A1  - Wolf, Julian
A1  - Prinz, Gabriele
A1  - Agostini, Hansjürgen
A1  - Schlunck, Günther
A1  - Wieghofer, Peter
A1  - Boneva, Stefaniya
A1  - Lange, Clemens
T1  - Immunosenescence in choroidal neovascularization (CNV) — Transcriptional profiling of naïve and CNV-associated retinal myeloid cells during aging
JF  - International Journal of Molecular Sciences
N2  - Immunosenescence is considered a possible factor in the development of age-related macular degeneration and choroidal neovascularization (CNV). However, age-related changes of myeloid cells (MCs), such as microglia and macrophages, in the healthy retina or during CNV formation are ill-defined. In this study, Cx3cr1-positive MCs were isolated by fluorescence-activated cell sorting from six-week (young) and two-year-old (old) Cx3cr1\(^{GFP/+}\) mice, both during physiological aging and laser-induced CNV development. High-throughput RNA-sequencing was performed to define the age-dependent transcriptional differences in MCs during physiological aging and CNV development, complemented by immunohistochemical characterization and the quantification of MCs, as well as CNV size measurements. These analyses revealed that myeloid cells change their transcriptional profile during both aging and CNV development. In the steady state, senescent MCs demonstrated an upregulation of factors contributing to cell proliferation and chemotaxis, such as Cxcl13 and Cxcl14, as well as the downregulation of microglial signature genes. During CNV formation, aged myeloid cells revealed a significant upregulation of angiogenic factors such as Arg1 and Lrg1 concomitant with significantly enlarged CNV and an increased accumulation of MCs in aged mice in comparison to young mice. Future studies need to clarify whether this observation is an epiphenomenon or a causal relationship to determine the role of immunosenescence in CNV formation.
KW  - age-related macular degeneration (AMD)
KW  - choroidal neovascularization (CNV)
KW  - aging
KW  - immunosenescence
KW  - microglia
KW  - myeloid cells
KW  - RNA-sequencing
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284342
SN  - 1422-0067
VL  - 22
IS  - 24
ER  - 
TY  - JOUR
A1  - Delgobo, Murilo
A1  - Heinrichs, Margarete
A1  - Hapke, Nils
A1  - Ashour, DiyaaElDin
A1  - Appel, Marc
A1  - Srivastava, Mugdha
A1  - Heckel, Tobias
A1  - Spyridopoulos, Ioakim
A1  - Hofmann, Ulrich
A1  - Frantz, Stefan
A1  - Ramos, Gustavo Campos
T1  - Terminally Differentiated CD4\(^+\) T Cells Promote Myocardial Inflammaging
JF  - Frontiers in Immunology
N2  - The cardiovascular and immune systems undergo profound and intertwined alterations with aging. Recent studies have reported that an accumulation of memory and terminally differentiated T cells in elderly subjects can fuel myocardial aging and boost the progression of heart diseases. Nevertheless, it remains unclear whether the immunological senescence profile is sufficient to cause age-related cardiac deterioration or merely acts as an amplifier of previous tissue-intrinsic damage. Herein, we sought to decompose the causality in this cardio-immune crosstalk by studying young mice harboring a senescent-like expanded CD4\(^+\) T cell compartment. Thus, immunodeficient NSG-DR1 mice expressing HLA-DRB1*01:01 were transplanted with human CD4\(^+\) T cells purified from matching donors that rapidly engrafted and expanded in the recipients without causing xenograft reactions. In the donor subjects, the CD4\(^+\) T cell compartment was primarily composed of naïve cells defined as CCR7\(^+\)CD45RO\(^-\). However, when transplanted into young lymphocyte-deficient mice, CD4\(^+\) T cells underwent homeostatic expansion, upregulated expression of PD-1 receptor and strongly shifted towards effector/memory (CCR7\(^-\) CD45RO\(^+\)) and terminally-differentiated phenotypes (CCR7\(^-\)CD45RO\(^-\)), as typically seen in elderly. Differentiated CD4\(^+\) T cells also infiltrated the myocardium of recipient mice at comparable levels to what is observed during physiological aging. In addition, young mice harboring an expanded CD4\(^+\) T cell compartment showed increased numbers of infiltrating monocytes, macrophages and dendritic cells in the heart. Bulk mRNA sequencing analyses further confirmed that expanding T-cells promote myocardial inflammaging, marked by a distinct age-related transcriptomic signature. Altogether, these data indicate that exaggerated CD4\(^+\) T-cell expansion and differentiation, a hallmark of the aging immune system, is sufficient to promote myocardial alterations compatible with inflammaging in juvenile healthy mice.
KW  - CD4+ T-cells
KW  - myocardial aging
KW  - inflammaging
KW  - NSG animals
KW  - immunosenescence
KW  - lymphocytes
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229612
SN  - 1664-3224
VL  - 12
ER  -