Disturbed natural killer cell homeostasis in the salivary gland enhances autoimmune pathology via IFN-γ in a mouse model of primary Sjögren’s syndrome
ObjectiveInnate lymphoid cells (ILCs), including natural killer (NK) cells, ILC1, ILC2, lymphoid tissue-inducer (LTi) cells, and ILC3 cell, play a key role in various immune responses. Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by chronic inflammation of exocrine glands,...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-10-01
|
| Series: | Frontiers in Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.1036787/full |
| _version_ | 1811338702155153408 |
|---|---|
| author | Mami Sato Rieko Arakaki Hiroaki Tawara Ruka Nagao Hidetaka Tanaka Kai Tamura Yuhki Kawahito Kunihiro Otsuka Aya Ushio Takaaki Tsunematsu Naozumi Ishimaru |
| author_facet | Mami Sato Rieko Arakaki Hiroaki Tawara Ruka Nagao Hidetaka Tanaka Kai Tamura Yuhki Kawahito Kunihiro Otsuka Aya Ushio Takaaki Tsunematsu Naozumi Ishimaru |
| author_sort | Mami Sato |
| collection | DOAJ |
| description | ObjectiveInnate lymphoid cells (ILCs), including natural killer (NK) cells, ILC1, ILC2, lymphoid tissue-inducer (LTi) cells, and ILC3 cell, play a key role in various immune responses. Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by chronic inflammation of exocrine glands, such as the lacrimal and salivary glands (SGs). The role of NK cells among ILCs in the pathogenesis of pSS is still unclear. In this study, the characteristics and subsets of NK cells in the salivary gland (SG) tissue were analyzed using a murine model of pSS.MethodsMultiple phenotypes and cytotoxic signature of the SG NK cells in control and pSS model mice were evaluated by flow cytometric analysis. Intracellular expression of interferon-γ (IFN-γ) among T cells and NK cells from the SG tissues was compared by in vitro experiments. In addition, pathological analysis was performed using anti-asialo-GM1 (ASGM1) antibody (Ab)-injected pSS model mice.ResultsThe number of conventional NK (cNK) cells in the SG of pSS model mice significantly increased compared with that in control mice at 6 weeks of age. The production level of IFN-γ was significantly higher in SG NK cells than in SG T cells. The depletion of NK cells by ASGM1 Ab altered the ratio of tissue resident NK (rNK) cells to cNK cells, which inhibited the injury to SG cells with the recovery of saliva secretion in pSS model mice.ConclusionThe results indicate that SG cNK cells may enhance the autoreactive response in the target organ by upregulating of IFN-γ, whereas SG rNK cells protect target cells against T cell cytotoxicity. Therefore, the activation process and multiple functions of NK cells in the target organ could be helpful to develop potential markers for determining autoimmune disease activity and target molecules for incurable immune disorders. |
| first_indexed | 2024-04-13T18:15:01Z |
| format | Article |
| id | doaj.art-56a4f49bc8b64752b478b705a065f41d |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-13T18:15:01Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-56a4f49bc8b64752b478b705a065f41d2022-12-22T02:35:43ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-10-01910.3389/fmed.2022.10367871036787Disturbed natural killer cell homeostasis in the salivary gland enhances autoimmune pathology via IFN-γ in a mouse model of primary Sjögren’s syndromeMami SatoRieko ArakakiHiroaki TawaraRuka NagaoHidetaka TanakaKai TamuraYuhki KawahitoKunihiro OtsukaAya UshioTakaaki TsunematsuNaozumi IshimaruObjectiveInnate lymphoid cells (ILCs), including natural killer (NK) cells, ILC1, ILC2, lymphoid tissue-inducer (LTi) cells, and ILC3 cell, play a key role in various immune responses. Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by chronic inflammation of exocrine glands, such as the lacrimal and salivary glands (SGs). The role of NK cells among ILCs in the pathogenesis of pSS is still unclear. In this study, the characteristics and subsets of NK cells in the salivary gland (SG) tissue were analyzed using a murine model of pSS.MethodsMultiple phenotypes and cytotoxic signature of the SG NK cells in control and pSS model mice were evaluated by flow cytometric analysis. Intracellular expression of interferon-γ (IFN-γ) among T cells and NK cells from the SG tissues was compared by in vitro experiments. In addition, pathological analysis was performed using anti-asialo-GM1 (ASGM1) antibody (Ab)-injected pSS model mice.ResultsThe number of conventional NK (cNK) cells in the SG of pSS model mice significantly increased compared with that in control mice at 6 weeks of age. The production level of IFN-γ was significantly higher in SG NK cells than in SG T cells. The depletion of NK cells by ASGM1 Ab altered the ratio of tissue resident NK (rNK) cells to cNK cells, which inhibited the injury to SG cells with the recovery of saliva secretion in pSS model mice.ConclusionThe results indicate that SG cNK cells may enhance the autoreactive response in the target organ by upregulating of IFN-γ, whereas SG rNK cells protect target cells against T cell cytotoxicity. Therefore, the activation process and multiple functions of NK cells in the target organ could be helpful to develop potential markers for determining autoimmune disease activity and target molecules for incurable immune disorders.https://www.frontiersin.org/articles/10.3389/fmed.2022.1036787/fullNK cellIFN-γT cellautoimmunitySjögren’s syndrome |
| spellingShingle | Mami Sato Rieko Arakaki Hiroaki Tawara Ruka Nagao Hidetaka Tanaka Kai Tamura Yuhki Kawahito Kunihiro Otsuka Aya Ushio Takaaki Tsunematsu Naozumi Ishimaru Disturbed natural killer cell homeostasis in the salivary gland enhances autoimmune pathology via IFN-γ in a mouse model of primary Sjögren’s syndrome Frontiers in Medicine NK cell IFN-γ T cell autoimmunity Sjögren’s syndrome |
| title | Disturbed natural killer cell homeostasis in the salivary gland enhances autoimmune pathology via IFN-γ in a mouse model of primary Sjögren’s syndrome |
| title_full | Disturbed natural killer cell homeostasis in the salivary gland enhances autoimmune pathology via IFN-γ in a mouse model of primary Sjögren’s syndrome |
| title_fullStr | Disturbed natural killer cell homeostasis in the salivary gland enhances autoimmune pathology via IFN-γ in a mouse model of primary Sjögren’s syndrome |
| title_full_unstemmed | Disturbed natural killer cell homeostasis in the salivary gland enhances autoimmune pathology via IFN-γ in a mouse model of primary Sjögren’s syndrome |
| title_short | Disturbed natural killer cell homeostasis in the salivary gland enhances autoimmune pathology via IFN-γ in a mouse model of primary Sjögren’s syndrome |
| title_sort | disturbed natural killer cell homeostasis in the salivary gland enhances autoimmune pathology via ifn γ in a mouse model of primary sjogren s syndrome |
| topic | NK cell IFN-γ T cell autoimmunity Sjögren’s syndrome |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.1036787/full |
| work_keys_str_mv | AT mamisato disturbednaturalkillercellhomeostasisinthesalivaryglandenhancesautoimmunepathologyviaifnginamousemodelofprimarysjogrenssyndrome AT riekoarakaki disturbednaturalkillercellhomeostasisinthesalivaryglandenhancesautoimmunepathologyviaifnginamousemodelofprimarysjogrenssyndrome AT hiroakitawara disturbednaturalkillercellhomeostasisinthesalivaryglandenhancesautoimmunepathologyviaifnginamousemodelofprimarysjogrenssyndrome AT rukanagao disturbednaturalkillercellhomeostasisinthesalivaryglandenhancesautoimmunepathologyviaifnginamousemodelofprimarysjogrenssyndrome AT hidetakatanaka disturbednaturalkillercellhomeostasisinthesalivaryglandenhancesautoimmunepathologyviaifnginamousemodelofprimarysjogrenssyndrome AT kaitamura disturbednaturalkillercellhomeostasisinthesalivaryglandenhancesautoimmunepathologyviaifnginamousemodelofprimarysjogrenssyndrome AT yuhkikawahito disturbednaturalkillercellhomeostasisinthesalivaryglandenhancesautoimmunepathologyviaifnginamousemodelofprimarysjogrenssyndrome AT kunihirootsuka disturbednaturalkillercellhomeostasisinthesalivaryglandenhancesautoimmunepathologyviaifnginamousemodelofprimarysjogrenssyndrome AT ayaushio disturbednaturalkillercellhomeostasisinthesalivaryglandenhancesautoimmunepathologyviaifnginamousemodelofprimarysjogrenssyndrome AT takaakitsunematsu disturbednaturalkillercellhomeostasisinthesalivaryglandenhancesautoimmunepathologyviaifnginamousemodelofprimarysjogrenssyndrome AT naozumiishimaru disturbednaturalkillercellhomeostasisinthesalivaryglandenhancesautoimmunepathologyviaifnginamousemodelofprimarysjogrenssyndrome |