Interleukin-15-dependent NKp46+ innate lymphoid cells control intestinal inflammation by recruiting inflammatory monocytes

Julie Schulthess; Bertrand Meresse; Emma Ramiro-Puig; Nicolas Montcuquet; Sylvie Darche; Bernadette Bègue; Frank Ruemmele; Christophe Combadière; James P Di Santo; Dominique Buzoni-Gatel; Nadine Cerf-Bensussan

doi:10.1016/j.immuni.2012.05.013

Interleukin-15-dependent NKp46+ innate lymphoid cells control intestinal inflammation by recruiting inflammatory monocytes

Immunity. 2012 Jul 27;37(1):108-21. doi: 10.1016/j.immuni.2012.05.013. Epub 2012 Jun 14.

Authors

Julie Schulthess¹, Bertrand Meresse, Emma Ramiro-Puig, Nicolas Montcuquet, Sylvie Darche, Bernadette Bègue, Frank Ruemmele, Christophe Combadière, James P Di Santo, Dominique Buzoni-Gatel, Nadine Cerf-Bensussan

Affiliation

¹ INSERM, U989, 75015 Paris, France; Université Paris Descartes, Paris Sorbonne Cité, Institut Imagine, France.

PMID: 22705105
DOI: 10.1016/j.immuni.2012.05.013

Abstract

With the goal in mind to define how interleukin-15 (IL-15) contributes to acute intestinal inflammation, we have used a mouse model of ileitis induced by oral infection with Toxoplasma gondii. We observed that a crosstalk between IL-15 and interleukin-18 (IL-18) promoted intestinal recruitment of inflammatory monocytes, where these cells participated in parasite control but also in tissue damage. A stromal source of IL-15 controlled the development of lamina propria NKp46(+)NK1.1(+) cells, whereas IL-18 produced during T. gondii infection stimulated their production of the chemokine CCL3. In turn, CCL3 attracted inflammatory monocytes via their chemokine receptor CCR1, which was indispensable for their recruitment into the inflamed gut. Collectively, these results identify the IL-15-dependent subset of intestinal NKp46(+) cells as an important source of CCL3, which can amplify intestinal inflammation via the recruitment of CCR1(+) inflammatory monocytes. Preliminary evidence suggests that this pathway might operate in Crohn's disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Animals
Antigens, Ly / metabolism*
Chemokine CCL3 / metabolism
Child
Crohn Disease / immunology
Crohn Disease / metabolism
Enteritis / immunology*
Enteritis / metabolism
Enteritis / parasitology
Humans
Interleukin-15 / genetics
Interleukin-15 / metabolism*
Interleukin-18 / immunology
Interleukin-18 / metabolism
Interleukin-7 Receptor alpha Subunit / metabolism
Intestinal Mucosa / immunology
Intestinal Mucosa / metabolism
Intestinal Mucosa / parasitology
Lymphocytes / immunology*
Lymphocytes / metabolism*
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Monocytes / immunology*
Monocytes / metabolism
NK Cell Lectin-Like Receptor Subfamily B / metabolism
Natural Cytotoxicity Triggering Receptor 1 / metabolism*
Receptors, CCR1 / metabolism
Th1 Cells / immunology
Th1 Cells / metabolism
Toxoplasma / immunology
Toxoplasma / metabolism

Substances

Antigens, Ly
Chemokine CCL3
Interleukin-15
Interleukin-18
Interleukin-7 Receptor alpha Subunit
Klrb1c protein, mouse
NK Cell Lectin-Like Receptor Subfamily B
Natural Cytotoxicity Triggering Receptor 1
Ncr1 protein, mouse
Receptors, CCR1