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Interleukin-22 produced by alveolar macrophages during activation of the innate immune response

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Abstract

Objective and design

Interleukin (IL)-22 is important for mucosal host defense. Whereas previous studies focus on lymphocytes as sources of IL-22, we determined whether IL-22 is produced by inflammatory cells in the lungs other than T-lymphocytes during the activation of the innate immune response.

Material, methods and treatment

Inflammatory cells in the lungs of Balb/c mice were primed by endotoxin (LPS, 10 μg) or peptidoglycan (PG, 40 μg) intranasally (3 days). After CD3 + cell depletion, lung homogenates were re-stimulated 24 h with LPS (100 ng/ml), PG (10 μg/ml), IL-23 (100 ng/ml) or vehicle. Human BAL macrophages were stimulated 24 h with PG (50 μg/ml) and IL-23 (100 ng/ml) or vehicle. The release of IL-22 was measured with ELISA and intracellular IL-22 with immunostaining. For statistics, either Dunnett or Students t test method was employed (n = 3–8).

Results

Re-stimulation in vitro increased concentrations of mouse IL-22 protein irrespective of priming in vivo. A majority of macrophages in mouse lung and BAL samples displayed immunostaining for IL-22. In analogy, human BAL macrophages released IL-22 protein, and a third of these cells displayed immunostaining for IL-22.

Conclusions

Alveolar macrophages can produce and release IL-22 during the activation of the innate immune response and thereby constitute a potentially important regulator of mucosal host defence in the lungs.

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Acknowledgments

The authors would like to thank Margaretha Smith, M.D., Helga Asgeirsdóttir, M.D., Åke Alfredsson, B.Sci., and Monika Crona, B.Sci., for technical assistance with the collection of the human BAL samples. This work was supported by the Swedish Heart–Lung Foundation (Grant Number 20070421), federal funding according to the ALF/LUA agreement, the Swedish Science Council (Grant Number K2008-57X-09048-19-3), King Gustav V’s and Queen Victoria’s Freemason Research Fund and Federal Funding at the Karolinska Institute.

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Authors and Affiliations

  1. Lung Immunology Group, Department of Internal Medicine and Clinical Nutrition/Respiratory Medicine and Allergology, Institute of Medicine, Sahlgrenska Academy at Gothenburg University, Guldhedsgatan 10A, Box 480, 405 30, Gothenburg, Sweden

    Marit Hansson, Elin Silverpil, Anders Lindén & Pernilla Glader

  2. The William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London, UK

    Elin Silverpil

  3. Unit for Lung and Airway Research, Physiology Division, Institute for Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

    Anders Lindén

Authors
  1. Marit Hansson
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  2. Elin Silverpil
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Correspondence to Marit Hansson.

Additional information

Responsible Editor: Graham Wallace.

Electronic supplementary material

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11_2013_608_MOESM1_ESM.pdf

Supporting material 1 Detection of immunostaining for IL-22 in CD3-depleted lung cells harvested from Balb/c mice exposed to PG (40 μg) for three consecutive days, and stimulated in vitro with IL-23 (100 ng/ml). Macrophages with positive immunostaining for F4/80 repeatedly showed immunostaining for IL-22 as well (n=3). Pictures show a typical result of double-staining for IL-22 and F4/80, single staining for IL-22 and F4/80, respectively, and isotype control antibody staining for both antibodies in 100x magnification (A) and 20x magnification (B) (PDF 554 kb)

11_2013_608_MOESM2_ESM.pdf

Supporting material 2 Detection of immunostaining for IL-22 in lung cells harvested from Balb/c mice exposed to PG (40 μg) for three consecutive days. Macrophages with positive immunostaining for F4/80 repeatedly showed immunostaining for IL-22 as well (n=3). Pictures show a typical result of double-staining for IL-22 and F4/80, single staining for IL-22 and F4/80, respectively, and isotype control antibody staining for both antibodies in 100x magnification (A) and 20x magnification (B) (PDF 566 kb)

11_2013_608_MOESM3_ESM.pdf

Supporting material 3 Detection of immunostaining for IL-22 in lung cells harvested from Balb/c mice exposed to PBS (vehicle) for three consecutive days. Macrophages with positive immunostaining for F4/80 repeatedly showed immunostaining for IL-22 as well (n=3). Pictures show a typical result of double-staining for IL-22 and F4/80, single staining for IL-22 and F4/80, respectively, and isotype control antibody staining for both antibodies in 100x magnification (A) and 20x magnification (B) (PDF 693 kb)

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Hansson, M., Silverpil, E., Lindén, A. et al. Interleukin-22 produced by alveolar macrophages during activation of the innate immune response. Inflamm. Res. 62, 561–569 (2013). https://doi.org/10.1007/s00011-013-0608-1

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  • DOI: https://doi.org/10.1007/s00011-013-0608-1

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