Age-Related Changes in Female Murine Reproductive Mucosa with respect to γδ T Cell Presence

Many studies have demonstrated a general decline and dysregulation in immune functions with age. It is not clear, however, how the aging affects the immune surveillance of the female reproductive tract (FRT) by γδ T cells, a unique population of T lymphocytes that was shown to regulate homeostasis o...

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Main Authors: Katarzyna Skulska, Anna Ewa Kędzierska, Małgorzata Krzyżowska, Grzegorz Chodaczek
Format: Article
Language:English
Published: Wiley 2023-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2023/3072573
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author Katarzyna Skulska
Anna Ewa Kędzierska
Małgorzata Krzyżowska
Grzegorz Chodaczek
author_facet Katarzyna Skulska
Anna Ewa Kędzierska
Małgorzata Krzyżowska
Grzegorz Chodaczek
author_sort Katarzyna Skulska
collection DOAJ
description Many studies have demonstrated a general decline and dysregulation in immune functions with age. It is not clear, however, how the aging affects the immune surveillance of the female reproductive tract (FRT) by γδ T cells, a unique population of T lymphocytes that was shown to regulate homeostasis of epithelial barriers. First, we analyzed γδ T cell presence in FRT in young (2 months) and old (18 months) wild-type (WT) C57BL/6 mice. We did not detect any changes in γδ T cell number nor distribution in the vaginas between the age groups, while in uteri, there was a twofold increase in γδ T cell number in aged mice. To check if γδ T lymphocytes regulate a metabolic and immune status of aging vaginal tissue, we compared the expression of 84 aging-associated genes in young and old WT and γδ T-cell-deficient (Tcrd-/-) mice. We discovered that only the Ltf (lactotransferrin) gene was downregulated in old Tcrd-/- mice. In both mouse strains, we found similar age-dependent changes in cytokine production upon vaginal inflammation due to Toll-like receptor 9 (TLR9) stimulation with CpG. With age in the vaginas, IL-1α and IL-17A levels increased while IL-6, IL-10, MCP-1, and IFNγ levels were diminished in response to CpG. Similar trends were observed in uteri. Interestingly, under the inflammatory state, the lack of γδ T cells in young individuals enhanced MCP-1 production in the vagina and decreased MCP-1 level in the uterus in old females. Our gene expression data point to an antimicrobial role of γδ T lymphocytes. The profile of secreted inflammatory cytokines shifted during aging toward the proinflammatory type, and γδ T cells played a modest fine-tuning role in immunoregulation in aged FRT. We believe this work expands our understanding of γδ T cell functions and the inflammaging in the murine reproductive epithelia.
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spelling doaj-art-de775b4ef5d6432aa60f7e5c6ade9cf52025-02-03T06:08:47ZengWileyJournal of Immunology Research2314-71562023-01-01202310.1155/2023/3072573Age-Related Changes in Female Murine Reproductive Mucosa with respect to γδ T Cell PresenceKatarzyna Skulska0Anna Ewa Kędzierska1Małgorzata Krzyżowska2Grzegorz Chodaczek3Łukasiewicz Research Network-PORT Polish Center for Technology DevelopmentŁukasiewicz Research Network-PORT Polish Center for Technology DevelopmentŁukasiewicz Research Network-PORT Polish Center for Technology DevelopmentŁukasiewicz Research Network-PORT Polish Center for Technology DevelopmentMany studies have demonstrated a general decline and dysregulation in immune functions with age. It is not clear, however, how the aging affects the immune surveillance of the female reproductive tract (FRT) by γδ T cells, a unique population of T lymphocytes that was shown to regulate homeostasis of epithelial barriers. First, we analyzed γδ T cell presence in FRT in young (2 months) and old (18 months) wild-type (WT) C57BL/6 mice. We did not detect any changes in γδ T cell number nor distribution in the vaginas between the age groups, while in uteri, there was a twofold increase in γδ T cell number in aged mice. To check if γδ T lymphocytes regulate a metabolic and immune status of aging vaginal tissue, we compared the expression of 84 aging-associated genes in young and old WT and γδ T-cell-deficient (Tcrd-/-) mice. We discovered that only the Ltf (lactotransferrin) gene was downregulated in old Tcrd-/- mice. In both mouse strains, we found similar age-dependent changes in cytokine production upon vaginal inflammation due to Toll-like receptor 9 (TLR9) stimulation with CpG. With age in the vaginas, IL-1α and IL-17A levels increased while IL-6, IL-10, MCP-1, and IFNγ levels were diminished in response to CpG. Similar trends were observed in uteri. Interestingly, under the inflammatory state, the lack of γδ T cells in young individuals enhanced MCP-1 production in the vagina and decreased MCP-1 level in the uterus in old females. Our gene expression data point to an antimicrobial role of γδ T lymphocytes. The profile of secreted inflammatory cytokines shifted during aging toward the proinflammatory type, and γδ T cells played a modest fine-tuning role in immunoregulation in aged FRT. We believe this work expands our understanding of γδ T cell functions and the inflammaging in the murine reproductive epithelia.http://dx.doi.org/10.1155/2023/3072573
spellingShingle Katarzyna Skulska
Anna Ewa Kędzierska
Małgorzata Krzyżowska
Grzegorz Chodaczek
Age-Related Changes in Female Murine Reproductive Mucosa with respect to γδ T Cell Presence
Journal of Immunology Research
title Age-Related Changes in Female Murine Reproductive Mucosa with respect to γδ T Cell Presence
title_full Age-Related Changes in Female Murine Reproductive Mucosa with respect to γδ T Cell Presence
title_fullStr Age-Related Changes in Female Murine Reproductive Mucosa with respect to γδ T Cell Presence
title_full_unstemmed Age-Related Changes in Female Murine Reproductive Mucosa with respect to γδ T Cell Presence
title_short Age-Related Changes in Female Murine Reproductive Mucosa with respect to γδ T Cell Presence
title_sort age related changes in female murine reproductive mucosa with respect to γδ t cell presence
url http://dx.doi.org/10.1155/2023/3072573
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AT małgorzatakrzyzowska agerelatedchangesinfemalemurinereproductivemucosawithrespecttogdtcellpresence
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