IL-25 elicits a multi-potent progenitor cell population that promotes Th2 cytokine responses
CD4 pos T helper (Th) 2 cells secrete interleukin (IL)-4, IL-5 and IL-13 and are required for immunity to gastrointestinal helminth infections 1 . However, Th2 cells also promote chronic inflammation associated with asthma and allergic disorders 2 . The non-hematopoietic cell-derived cytokines thymi...
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Published in | Nature (London) Vol. 464; no. 7293; pp. 1362 - 1366 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
03.03.2010
|
Online Access | Get full text |
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Abstract | CD4
pos
T helper (Th) 2 cells secrete interleukin (IL)-4, IL-5 and IL-13 and are required for immunity to gastrointestinal helminth infections
1
. However, Th2 cells also promote chronic inflammation associated with asthma and allergic disorders
2
. The non-hematopoietic cell-derived cytokines thymic stromal lymphopoietin (TSLP), IL-33 and IL-25 (IL-17E) have been implicated in inducing Th2 cell-dependent inflammation at mucosal sites
3
-
6
, but how these cytokines influence innate immune responses remains poorly defined. Here we show that IL-25, a member of the IL-17 cytokine family, promotes the accumulation of a lineage negative (Lin
neg
) multi-potent progenitor (MPP) cell population in the gut-associated lymphoid tissue (GALT) that promotes Th2 cytokine responses. The IL-25-elicited cell population, termed MPP
type2
cells, was defined by expression of Sca-1 and intermediate expression of c-kit (c-kit
int
) and exhibited multi-potent capacity, giving rise to cells of monocyte/macrophage and granulocyte lineages both
in vitro
and
in vivo
. Progeny of MPP
type2
cells were competent antigen presenting cells and adoptive transfer of MPP
type2
cells could promote Th2 cytokine responses and confer protective immunity to helminth infection in normally susceptible
Il17e
-/-
mice. The ability of IL-25 to induce the emergence of an MPP
type2
cell population identifies a link between the IL-17 cytokine family and extramedullary hematopoiesis and suggests a previously unrecognized innate immune pathway that promotes Th2 cytokine responses at mucosal sites. |
---|---|
AbstractList | CD4
pos
T helper (Th) 2 cells secrete interleukin (IL)-4, IL-5 and IL-13 and are required for immunity to gastrointestinal helminth infections
1
. However, Th2 cells also promote chronic inflammation associated with asthma and allergic disorders
2
. The non-hematopoietic cell-derived cytokines thymic stromal lymphopoietin (TSLP), IL-33 and IL-25 (IL-17E) have been implicated in inducing Th2 cell-dependent inflammation at mucosal sites
3
-
6
, but how these cytokines influence innate immune responses remains poorly defined. Here we show that IL-25, a member of the IL-17 cytokine family, promotes the accumulation of a lineage negative (Lin
neg
) multi-potent progenitor (MPP) cell population in the gut-associated lymphoid tissue (GALT) that promotes Th2 cytokine responses. The IL-25-elicited cell population, termed MPP
type2
cells, was defined by expression of Sca-1 and intermediate expression of c-kit (c-kit
int
) and exhibited multi-potent capacity, giving rise to cells of monocyte/macrophage and granulocyte lineages both
in vitro
and
in vivo
. Progeny of MPP
type2
cells were competent antigen presenting cells and adoptive transfer of MPP
type2
cells could promote Th2 cytokine responses and confer protective immunity to helminth infection in normally susceptible
Il17e
-/-
mice. The ability of IL-25 to induce the emergence of an MPP
type2
cell population identifies a link between the IL-17 cytokine family and extramedullary hematopoiesis and suggests a previously unrecognized innate immune pathway that promotes Th2 cytokine responses at mucosal sites. |
Author | Kleinschek, Melanie A. Budelsky, Alison L. Kastelein, Robert A. Saenz, Steven A. Perrigoue, Jacqueline G. Spencer, Sean P. Artis, David Kambayashi, Taku Bhandoola, Avinash Siracusa, Mark C. Tocker, Joel E. Urban, Joseph F. |
AuthorAffiliation | 5 Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA 2 Diet, Genomics, & Immunology Lab, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, MD 20705, USA 4 Discovery Research, Schering-Plough Biopharma, Palo Alto, CA 94304, USA 3 Department of Inflammation Research, Amgen, Seattle, WA 98119, USA 1 Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA |
AuthorAffiliation_xml | – name: 3 Department of Inflammation Research, Amgen, Seattle, WA 98119, USA – name: 4 Discovery Research, Schering-Plough Biopharma, Palo Alto, CA 94304, USA – name: 5 Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA – name: 1 Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA – name: 2 Diet, Genomics, & Immunology Lab, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, MD 20705, USA |
Author_xml | – sequence: 1 givenname: Steven A. surname: Saenz fullname: Saenz, Steven A. organization: Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA Diet, Genomics, & Immunology Lab, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, MD 20705, USA Department of Inflammation Research, Amgen, Seattle, WA 98119, USA Discovery Research, Schering-Plough Biopharma, Palo Alto, CA 94304, USA Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA – sequence: 2 givenname: Mark C. surname: Siracusa fullname: Siracusa, Mark C. organization: Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA Diet, Genomics, & Immunology Lab, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, MD 20705, USA Department of Inflammation Research, Amgen, Seattle, WA 98119, USA Discovery Research, Schering-Plough Biopharma, Palo Alto, CA 94304, USA Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA – sequence: 3 givenname: Jacqueline G. surname: Perrigoue fullname: Perrigoue, Jacqueline G. organization: Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA Diet, Genomics, & Immunology Lab, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, MD 20705, USA Department of Inflammation Research, Amgen, Seattle, WA 98119, USA Discovery Research, Schering-Plough Biopharma, Palo Alto, CA 94304, USA Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA – sequence: 4 givenname: Sean P. surname: Spencer fullname: Spencer, Sean P. organization: Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA Diet, Genomics, & Immunology Lab, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, MD 20705, USA Department of Inflammation Research, Amgen, Seattle, WA 98119, USA Discovery Research, Schering-Plough Biopharma, Palo Alto, CA 94304, USA Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA – sequence: 5 givenname: Joseph F. surname: Urban fullname: Urban, Joseph F. organization: Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA Diet, Genomics, & Immunology Lab, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, MD 20705, USA Department of Inflammation Research, Amgen, Seattle, WA 98119, USA Discovery Research, Schering-Plough Biopharma, Palo Alto, CA 94304, USA Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA – sequence: 6 givenname: Joel E. surname: Tocker fullname: Tocker, Joel E. organization: Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA Diet, Genomics, & Immunology Lab, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, MD 20705, USA Department of Inflammation Research, Amgen, Seattle, WA 98119, USA Discovery Research, Schering-Plough Biopharma, Palo Alto, CA 94304, USA Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA – sequence: 7 givenname: Alison L. surname: Budelsky fullname: Budelsky, Alison L. organization: Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA Diet, Genomics, & Immunology Lab, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, MD 20705, USA Department of Inflammation Research, Amgen, Seattle, WA 98119, USA Discovery Research, Schering-Plough Biopharma, Palo Alto, CA 94304, USA Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA – sequence: 8 givenname: Melanie A. surname: Kleinschek fullname: Kleinschek, Melanie A. organization: Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA Diet, Genomics, & Immunology Lab, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, MD 20705, USA Department of Inflammation Research, Amgen, Seattle, WA 98119, USA Discovery Research, Schering-Plough Biopharma, Palo Alto, CA 94304, USA Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA – sequence: 9 givenname: Robert A. surname: Kastelein fullname: Kastelein, Robert A. organization: Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA Diet, Genomics, & Immunology Lab, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, MD 20705, USA Department of Inflammation Research, Amgen, Seattle, WA 98119, USA Discovery Research, Schering-Plough Biopharma, Palo Alto, CA 94304, USA Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA – sequence: 10 givenname: Taku surname: Kambayashi fullname: Kambayashi, Taku organization: Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA Diet, Genomics, & Immunology Lab, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, MD 20705, USA Department of Inflammation Research, Amgen, Seattle, WA 98119, USA Discovery Research, Schering-Plough Biopharma, Palo Alto, CA 94304, USA Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA – sequence: 11 givenname: Avinash surname: Bhandoola fullname: Bhandoola, Avinash organization: Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA Diet, Genomics, & Immunology Lab, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, MD 20705, USA Department of Inflammation Research, Amgen, Seattle, WA 98119, USA Discovery Research, Schering-Plough Biopharma, Palo Alto, CA 94304, USA Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA – sequence: 12 givenname: David surname: Artis fullname: Artis, David organization: Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA Diet, Genomics, & Immunology Lab, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, MD 20705, USA Department of Inflammation Research, Amgen, Seattle, WA 98119, USA Discovery Research, Schering-Plough Biopharma, Palo Alto, CA 94304, USA Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA |
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pos
T helper (Th) 2 cells secrete interleukin (IL)-4, IL-5 and IL-13 and are required for immunity to gastrointestinal helminth infections
1
. However, Th2... |
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Title | IL-25 elicits a multi-potent progenitor cell population that promotes Th2 cytokine responses |
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