Cigarette smoke silences innate lymphoid cell function and facilitates an exacerbated type I interleukin-33-dependent response to infection - PubMed (original) (raw)

. 2015 Mar 17;42(3):566-79.

doi: 10.1016/j.immuni.2015.02.011.

Jonathan S Silver 1, Caroline Sanden 2, Zheng Liu 3, Aaron A Berlin 1, Natalie White 1, Michiko Mori 2, Tuyet-Hang Pham 3, Christine K Ward 3, Gerard J Criner 4, Nathaniel Marchetti 4, Tomas Mustelin 1, Jonas S Erjefalt 2, Roland Kolbeck 1, Alison A Humbles 5

Affiliations

• PMID: 25786179
• DOI: 10.1016/j.immuni.2015.02.011

Free article

Cigarette smoke silences innate lymphoid cell function and facilitates an exacerbated type I interleukin-33-dependent response to infection

Jennifer Kearley et al. Immunity. 2015.

Free article

Abstract

Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease and is presumed to be central to the altered responsiveness to recurrent infection in these patients. We examined the effects of smoke priming underlying the exacerbated response to viral infection in mice. Lack of interleukin-33 (IL-33) signaling conferred complete protection during exacerbation and prevented enhanced inflammation and exaggerated weight loss. Mechanistically, smoke was required to upregulate epithelial-derived IL-33 and simultaneously alter the distribution of the IL-33 receptor ST2. Specifically, smoke decreased ST2 expression on group 2 innate lymphoid cells (ILC2s) while elevating ST2 expression on macrophages and natural killer (NK) cells, thus altering IL-33 responsiveness within the lung. Consequently, upon infection and release, increased local IL-33 significantly amplified type I proinflammatory responses via synergistic modulation of macrophage and NK cell function. Therefore, in COPD, smoke alters the lung microenvironment to facilitate an alternative IL-33-dependent exaggerated proinflammatory response to infection, exacerbating disease.

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Comment in

• Cigarette smoke resets the Alarmin IL-33 in COPD.
  Liew FY. Liew FY. Immunity. 2015 Mar 17;42(3):401-3. doi: 10.1016/j.immuni.2015.02.014. Immunity. 2015. PMID: 25786171
• Cytokines: Where there's smoke, there's fire.
  Bird L. Bird L. Nat Rev Immunol. 2015 May;15(5):268-9. doi: 10.1038/nri3852. Epub 2015 Apr 17. Nat Rev Immunol. 2015. PMID: 25882244 No abstract available.

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