دورية أكاديمية
Gender Disparity Impacts on Thymus Aging and LHRH Receptor Antagonist-Induced Thymic Reconstitution Following Chemotherapeutic Damage.
| العنوان: | Gender Disparity Impacts on Thymus Aging and LHRH Receptor Antagonist-Induced Thymic Reconstitution Following Chemotherapeutic Damage. |
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| المؤلفون: | Hun ML; Thymus Development, Ageing and T Cell Regeneration Laboratory, Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University Clayton, Melbourne, VIC, Australia., Wong K; Thymus Development, Ageing and T Cell Regeneration Laboratory, Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University Clayton, Melbourne, VIC, Australia., Gunawan JR; Thymus Development, Ageing and T Cell Regeneration Laboratory, Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University Clayton, Melbourne, VIC, Australia., Alsharif A; Thymus Development, Ageing and T Cell Regeneration Laboratory, Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University Clayton, Melbourne, VIC, Australia., Quinn K; Quinn Laboratory, Translational Immunology and Nanotechnology Research Program, School of Health and Biomedical Research, RMIT University, Melbourne, VIC, Australia., Chidgey AP; Thymus Development, Ageing and T Cell Regeneration Laboratory, Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University Clayton, Melbourne, VIC, Australia. |
| المصدر: | Frontiers in immunology [Front Immunol] 2020 Mar 03; Vol. 11, pp. 302. Date of Electronic Publication: 2020 Mar 03 (Print Publication: 2020). |
| نوع المنشور: | Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | Sex Characteristics*, Aging/*immunology , Antineoplastic Agents, Alkylating/*toxicity , Cyclophosphamide/*toxicity , Epithelial Cells/*drug effects , Oligopeptides/*therapeutic use , Receptors, LHRH/*antagonists & inhibitors , Thymocytes/*drug effects , Thymus Gland/*drug effects, Animals ; Atrophy ; Cell Count ; Cells, Cultured ; Female ; Follicle Stimulating Hormone/blood ; Gonadal Steroid Hormones/physiology ; Luteinizing Hormone/blood ; Male ; Mice ; Mice, Inbred C57BL ; Oligopeptides/pharmacology ; Self Tolerance ; Sexual Maturation ; Stromal Cells ; Thymus Gland/growth & development ; Thymus Gland/pathology ; Transcription Factors/biosynthesis ; Transcription Factors/genetics ; AIRE Protein |
| مستخلص: | One of the main consequences of thymus aging is the decrease in naïve T cell output. This condition accelerates at the onset of puberty, and presents as a major clinical complication for cancer patients who require cytoablative therapy. Specifically, the extensive use of chemotherapeutics, such as cyclophosphamide, in such treatments damage thymic structure and eliminate the existing naïve T cell repertoire. The resulting immunodeficiency can lead to increased incidence of opportunistic infections, tumor growth relapse and/or autoimmune diseases, particularly in older patients. Thus, strategies aimed at rejuvenating the aged thymus following chemotherapeutic damage are required. Previous studies have revealed that sex hormone deprivation in male mice is capable of regenerating the thymic microenvironment following chemotherapy treatment, however, further investigation is crucial to identify gender-based differences, and the molecular mechanisms involved during thymus regeneration. Through phenotypic analyzes, we identified gender-specific alterations in thymocytes and thymic epithelial cell (TEC) subsets from the onset of puberty. By middle-age, females presented with a higher number of thymocytes in comparison to males, yet a decrease in their Aire + medullary TEC/thymocyte ratio was observed. This reduction could be associated with an increased risk of autoimmune disease in middle-aged women. Given the concurrent increase in female Aire + cTEC/thymocyte ratio, we proposed that there may be an impediment in Aire + mTEC hi differentiation, and Aire + cTEC hi as its upstream precursor. The regenerative effects of LHRH receptor antagonist, degarelix, on TEC subsets was also less pronounced in middle-aged females compared to males, possibly due to slower progression of thymic involution in the former, which presented with greater TEC hi proportions. Furthermore, following cyclophosphamide treatment, degarelix enhanced thymocyte and mature TEC subset recovery, with faster recovery kinetics observed in females. These events were found to involve both reactivation and proliferation of thymic epithelial progenitor cells. Taken together, the findings from this study portray a relationship between gender disparity and thymus aging, and highlight the potential benefits of LHRH receptor antagonist treatment for thymic regeneration. Further research is required, however, to determine how gender may impact on the mechanisms underpinning these events. (Copyright © 2020 Hun, Wong, Gunawan, Alsharif, Quinn and Chidgey.) |
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| فهرسة مساهمة: | Keywords: aging; chemotherapy; gender; luteinizing hormone-releasing hormone; regeneration; sex hormone deprivation; thymic epithelial cell; thymus |
| المشرفين على المادة: | 0 (Antineoplastic Agents, Alkylating) 0 (Gonadal Steroid Hormones) 0 (Oligopeptides) 0 (Receptors, LHRH) 0 (Transcription Factors) 0 (acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide) 8N3DW7272P (Cyclophosphamide) 9002-67-9 (Luteinizing Hormone) 9002-68-0 (Follicle Stimulating Hormone) |
| تواريخ الأحداث: | Date Created: 20200321 Date Completed: 20210315 Latest Revision: 20231213 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC7062683 |
| DOI: | 10.3389/fimmu.2020.00302 |
| PMID: | 32194555 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2020.00302 |