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postgraduate thesis: Leptin modulates B cell responses against influenza infection

TitleLeptin modulates B cell responses against influenza infection
Authors
Issue Date2015
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Chen, M. [陳淼]. (2015). Leptin modulates B cell responses against influenza infection. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5689302
AbstractLeptin, a protein hormone mainly produced by adipocytes, is encoded by obse (ob) gene. The significance of leptin to regulate metabolism and neuroendorine as well as other physiological functions has been well defined. Leptin is critically involved in regulating energy metabolism and neuroendocrine function. As a cytokine, leptin exerts important function in regulating the lymphopoiesis and hematopoiesis. Although the roles of leptin in regulating B-2 cell function in adaptive immune response during autoimmune diseases have been described, little study reveals whether and how leptin regulates B-1 cell function in innate immune response, particularly during influenza infection. In this study, increased leptin concentration has been examined in the bronchoalveolar lavage fluid (BLF) and sera of mice with H1N1 influenza infection. Conversely, leptin receptor deficient db/db mice exhibited much lower survival rate and more severe lung destruction. Previous studies demonstrated the critical role of B-1 cells upon influenza virus infection. This was also supported in the present study by the evidence of significantly increased mortality in a B-1 cell depleted mouse model upon H1N1 infection. However, whether leptin deficiency impaired the function of B-1 cells against H1N1 infection is unknown. In culture, leptin enhanced the viability of B-1 cells in dose dependent manner. Moreover, leptin promoted IgM production by activated B-1 cell, whereas leptin had no impact on B-1 cell proliferation. Consistently, impaired local production of IgM or IgG in the BLF of db/db mice upon H1N1 infection were observed Further, db/db mice showed more severe lung injury than wild type mice, indicating that leptin may potentially restrain overt immune responses in local tissue. Consequently, adoptive transfer of B-1 cell from wild type to db/db mice showed improved survival rate and ameliorated lung damage. Further studies revealed the pulmonary γδT cells as the main infiltrating-T cell subset and the major source of IL-17 in local tissue. A higher frequency of pulmonary IL-17 secreting γδT cells (γδT-17) in db/db mice was found. In addition, db/db mice received WT, but not IL-17-/- γδT cells transfer resulted in much lower survival rate and increased tissue damage. By contrast, B-1 cells transfer significantly reduced pulmonary γδT-17 cell response and ameliorated lung damage in an IL-10 dependent manner. Finally, leptin deficiency did not affect γδT-17 cell, but reduced production of IL-10 in pulmonary B cells upon H1N1 influenza infection, indicating the intrinsic requirement of leptin in B-1 cells derived IL-10 to suppress overt immune dysregulation. Taken together, these results identified that leptin play immune modulatory role in B-1 cell response upon influenza virus infection, which contributed to further understanding of B-1 cell response in host defense.
DegreeMaster of Philosophy
SubjectLeptin
Influenza - Immunological aspects
Dept/ProgramPathology
Persistent Identifierhttp://hdl.handle.net/10722/222403

 

DC FieldValueLanguage
dc.contributor.authorChen, Miao-
dc.contributor.author陳淼-
dc.date.accessioned2016-01-13T01:23:31Z-
dc.date.available2016-01-13T01:23:31Z-
dc.date.issued2015-
dc.identifier.citationChen, M. [陳淼]. (2015). Leptin modulates B cell responses against influenza infection. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5689302-
dc.identifier.urihttp://hdl.handle.net/10722/222403-
dc.description.abstractLeptin, a protein hormone mainly produced by adipocytes, is encoded by obse (ob) gene. The significance of leptin to regulate metabolism and neuroendorine as well as other physiological functions has been well defined. Leptin is critically involved in regulating energy metabolism and neuroendocrine function. As a cytokine, leptin exerts important function in regulating the lymphopoiesis and hematopoiesis. Although the roles of leptin in regulating B-2 cell function in adaptive immune response during autoimmune diseases have been described, little study reveals whether and how leptin regulates B-1 cell function in innate immune response, particularly during influenza infection. In this study, increased leptin concentration has been examined in the bronchoalveolar lavage fluid (BLF) and sera of mice with H1N1 influenza infection. Conversely, leptin receptor deficient db/db mice exhibited much lower survival rate and more severe lung destruction. Previous studies demonstrated the critical role of B-1 cells upon influenza virus infection. This was also supported in the present study by the evidence of significantly increased mortality in a B-1 cell depleted mouse model upon H1N1 infection. However, whether leptin deficiency impaired the function of B-1 cells against H1N1 infection is unknown. In culture, leptin enhanced the viability of B-1 cells in dose dependent manner. Moreover, leptin promoted IgM production by activated B-1 cell, whereas leptin had no impact on B-1 cell proliferation. Consistently, impaired local production of IgM or IgG in the BLF of db/db mice upon H1N1 infection were observed Further, db/db mice showed more severe lung injury than wild type mice, indicating that leptin may potentially restrain overt immune responses in local tissue. Consequently, adoptive transfer of B-1 cell from wild type to db/db mice showed improved survival rate and ameliorated lung damage. Further studies revealed the pulmonary γδT cells as the main infiltrating-T cell subset and the major source of IL-17 in local tissue. A higher frequency of pulmonary IL-17 secreting γδT cells (γδT-17) in db/db mice was found. In addition, db/db mice received WT, but not IL-17-/- γδT cells transfer resulted in much lower survival rate and increased tissue damage. By contrast, B-1 cells transfer significantly reduced pulmonary γδT-17 cell response and ameliorated lung damage in an IL-10 dependent manner. Finally, leptin deficiency did not affect γδT-17 cell, but reduced production of IL-10 in pulmonary B cells upon H1N1 influenza infection, indicating the intrinsic requirement of leptin in B-1 cells derived IL-10 to suppress overt immune dysregulation. Taken together, these results identified that leptin play immune modulatory role in B-1 cell response upon influenza virus infection, which contributed to further understanding of B-1 cell response in host defense.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.subject.lcshLeptin-
dc.subject.lcshInfluenza - Immunological aspects-
dc.titleLeptin modulates B cell responses against influenza infection-
dc.typePG_Thesis-
dc.identifier.hkulb5689302-
dc.description.thesisnameMaster of Philosophy-
dc.description.thesislevelMaster-
dc.description.thesisdisciplinePathology-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b5689302-

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