【讨论】Innate immunity: 'Natural helper' cells identified
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A recent paper published in Nature describes a new population of innate lymphocytes that are found in a previously unrecognized lymphoid structure associated with adipose tissue. The authors propose that these T helper 2 (TH2)-type innate lymphocytes be termed 'natural helper' cells.
In this study, the authors identified a lymphoid structure in the peritoneal cavity of mice composed of clusters of lymphocytes that was distinct from other lymphoid tissues and surrounded by adipose tissues. These structures were also found in the adipose tissues around the kidney and genitalia, as well as in the human mesentery, and were termed fat-associated lymphoid clusters (FALCs). Within these structures, KIT+SCA1+ cells were identified that do not express lineage (LIN) markers but express interleukin-7 receptor-α (IL-7Rα) and ST2 (a subunit of IL-33R), along with several other cell surface molecules. Further analysis showed that these cells are of lymphoid lineage but are distinct from B and T cells, natural killer cells, lymphoid-tissue inducer cells and IL-22-producing NKp46+ cells.
Stem cell factor and IL-7 were shown to support the survival of FALC KIT+SCA1+ cells, and IL-2 induced cell proliferation and the production of the TH2-type cytokines IL-5, IL-6 and IL-13 in vitro. These cells also produced TH2-type cytokines, as well as low levels of interferon-γ, in response to PMA (phorbol 12-myristate 13-acetate) plus ionomycin, and incubation with IL-33 or IL-2 plus IL-25 induced high levels of IL-5 and IL-13 production.
Furthermore, FALC KIT+SCA1+ cells support the proliferation of B-1 but not B-2 B cells and have a helper function for IgA production in vitro. To confirm this observation in vivo, the authors transferred B-1 B cells with or without FALC KIT+SCA1+ cells into immunodeficient mice and found that FALC KIT+SCA1+ cells enhanced the proliferation of B-1 B cells. In addition, FALC KIT+SCA1+ cells were shown to be the main producers of IL-5 and IL-13 in vivo in response to IL-33, and mice lacking these cells did not produce IL-5 and IL-13 or induce goblet cell hyperplasia in response to infection with the helminth Nippostrongylus brasiliensis.
So, FALC KIT+SCA1+ cells are a newly described innate lymphocyte population present in FALCs that produce high levels of TH2-type cytokines, support B-1 B cell proliferation and promote goblet cell hyperplasia in response to helminth infection.
原文
Innate production of TH2 cytokines by adipose tissue-associated c-Kit+Sca-1+ lymphoid cells
Abstract
Innate immune responses are important in combating various microbes during the early phases of infection. Natural killer (NK) cells are innate lymphocytes that, unlike T and B lymphocytes, do not express antigen receptors but rapidly exhibit cytotoxic activities against virus-infected cells and produce various cytokines1, 2. Here we report a new type of innate lymphocyte present in a novel lymphoid structure associated with adipose tissues in the peritoneal cavity. These cells do not express lineage (Lin) markers but do express c-Kit, Sca-1 (also known as Ly6a), IL7R and IL33R. Similar lymphoid clusters were found in both human and mouse mesentery and we term this tissue ‘FALC’ (fat-associated lymphoid cluster). FALC Lin-c-Kit+Sca-1+ cells are distinct from lymphoid progenitors3 and lymphoid tissue inducer cells4. These cells proliferate in response to IL2 and produce large amounts of TH2 cytokines such as IL5, IL6 and IL13. IL5 and IL6 regulate B-cell antibody production and self-renewal of B1 cells5, 6, 7. Indeed, FALC Lin-c-Kit+Sca-1+ cells support the self-renewal of B1 cells and enhance IgA production. IL5 and IL13 mediate allergic inflammation and protection against helminth infection8, 9. After helminth infection and in response to IL33, FALC Lin-c-Kit+Sca-1+ cells produce large amounts of IL13, which leads to goblet cell hyperplasia—a critical step for helminth expulsion. In mice devoid of FALC Lin-c-Kit+Sca-1+ cells, such goblet cell hyperplasia was not induced. Thus, FALC Lin-c-Kit+Sca-1+ cells are TH2-type innate lymphocytes, and we propose that these cells be called ‘natural helper cells’.
In this study, the authors identified a lymphoid structure in the peritoneal cavity of mice composed of clusters of lymphocytes that was distinct from other lymphoid tissues and surrounded by adipose tissues. These structures were also found in the adipose tissues around the kidney and genitalia, as well as in the human mesentery, and were termed fat-associated lymphoid clusters (FALCs). Within these structures, KIT+SCA1+ cells were identified that do not express lineage (LIN) markers but express interleukin-7 receptor-α (IL-7Rα) and ST2 (a subunit of IL-33R), along with several other cell surface molecules. Further analysis showed that these cells are of lymphoid lineage but are distinct from B and T cells, natural killer cells, lymphoid-tissue inducer cells and IL-22-producing NKp46+ cells.
Stem cell factor and IL-7 were shown to support the survival of FALC KIT+SCA1+ cells, and IL-2 induced cell proliferation and the production of the TH2-type cytokines IL-5, IL-6 and IL-13 in vitro. These cells also produced TH2-type cytokines, as well as low levels of interferon-γ, in response to PMA (phorbol 12-myristate 13-acetate) plus ionomycin, and incubation with IL-33 or IL-2 plus IL-25 induced high levels of IL-5 and IL-13 production.
Furthermore, FALC KIT+SCA1+ cells support the proliferation of B-1 but not B-2 B cells and have a helper function for IgA production in vitro. To confirm this observation in vivo, the authors transferred B-1 B cells with or without FALC KIT+SCA1+ cells into immunodeficient mice and found that FALC KIT+SCA1+ cells enhanced the proliferation of B-1 B cells. In addition, FALC KIT+SCA1+ cells were shown to be the main producers of IL-5 and IL-13 in vivo in response to IL-33, and mice lacking these cells did not produce IL-5 and IL-13 or induce goblet cell hyperplasia in response to infection with the helminth Nippostrongylus brasiliensis.
So, FALC KIT+SCA1+ cells are a newly described innate lymphocyte population present in FALCs that produce high levels of TH2-type cytokines, support B-1 B cell proliferation and promote goblet cell hyperplasia in response to helminth infection.
原文
Innate production of TH2 cytokines by adipose tissue-associated c-Kit+Sca-1+ lymphoid cells
Abstract
Innate immune responses are important in combating various microbes during the early phases of infection. Natural killer (NK) cells are innate lymphocytes that, unlike T and B lymphocytes, do not express antigen receptors but rapidly exhibit cytotoxic activities against virus-infected cells and produce various cytokines1, 2. Here we report a new type of innate lymphocyte present in a novel lymphoid structure associated with adipose tissues in the peritoneal cavity. These cells do not express lineage (Lin) markers but do express c-Kit, Sca-1 (also known as Ly6a), IL7R and IL33R. Similar lymphoid clusters were found in both human and mouse mesentery and we term this tissue ‘FALC’ (fat-associated lymphoid cluster). FALC Lin-c-Kit+Sca-1+ cells are distinct from lymphoid progenitors3 and lymphoid tissue inducer cells4. These cells proliferate in response to IL2 and produce large amounts of TH2 cytokines such as IL5, IL6 and IL13. IL5 and IL6 regulate B-cell antibody production and self-renewal of B1 cells5, 6, 7. Indeed, FALC Lin-c-Kit+Sca-1+ cells support the self-renewal of B1 cells and enhance IgA production. IL5 and IL13 mediate allergic inflammation and protection against helminth infection8, 9. After helminth infection and in response to IL33, FALC Lin-c-Kit+Sca-1+ cells produce large amounts of IL13, which leads to goblet cell hyperplasia—a critical step for helminth expulsion. In mice devoid of FALC Lin-c-Kit+Sca-1+ cells, such goblet cell hyperplasia was not induced. Thus, FALC Lin-c-Kit+Sca-1+ cells are TH2-type innate lymphocytes, and we propose that these cells be called ‘natural helper cells’.
