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IL-22Ra1 is induced during influenza infection by direct and indirect TLR3 induction of STAT1.
Respir Res 2019; 20(1):184RR

Abstract

BACKGROUND

Influenza attacks the epithelium of the lung, causing cell death and disruption of the epithelial barrier leading to fluid buildup in the lung and impairment of gas exchange. Limited treatment options for severe influenza pneumonia prioritize the need for the discovery of effective therapies. IL-22 is a cytokine that promotes tissue integrity and has strong promise as a treatment option. While research has been focused on the cytokine itself, there is limited understanding of the regulation of the IL-22 receptor (IL-22Ra1) at the epithelial surface during infection.

METHODS

IL-22Ra1 levels were measured by qRT-PCR, western blot and immunofluorescence following H1N1 influenza infection (A/PR/8/34 H1N1) or synthetic TLR3 mimetic, Poly (I:C). Regulation of the receptor was determined using STAT inhibitors (STAT1, STAT3 and PanSTAT inhibitors), TLR3 inhibition, and neutralization of interferon alpha receptor 2 (IFNAR2). Significance was determined by a p-value of greater than 0.05. Significance between two groups was measured using unpaired t-test and significance between more than two groups was measured using one-way ANOVA with Tukey Multiple Comparison Test.

RESULTS

Here we show both in vivo and in vitro that IL-22Ra1 was induced as early as 24 h after influenza (H1N1 PR8) infection. This induction was triggered by toll-like receptor 3 (TLR3) as a TLR3 mimetic [Poly (I:C)] also induced IL-22Ra1 and inhibition of endosomal formation required for TLR3 function inhibited this process. This upregulation was dependent upon IFNβ signaling through STAT1. Importantly, induction of IL-22Ra1 significantly increased IL-22 signaling as evidenced by pSTAT3 levels following IL-22 treatment.

CONCLUSION

Collectively, these data suggest epithelial cells may optimize the beneficial effects of IL-22 through the induction of the IL-22 receptor during viral infection in the lung.

Authors+Show Affiliations

Department of Medicine, Pulmonary Diseases, Critical Care & Environmental Medicine, Tulane University School of Medicine, 1430 Tulane Ave. Mail code sl279, New Orleans, LA, 70112, USA.Department of Medicine, Pulmonary Diseases, Critical Care & Environmental Medicine, Tulane University School of Medicine, 1430 Tulane Ave. Mail code sl279, New Orleans, LA, 70112, USA.Department of Medicine, Pulmonary Diseases, Critical Care & Environmental Medicine, Tulane University School of Medicine, 1430 Tulane Ave. Mail code sl279, New Orleans, LA, 70112, USA.Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, One Children's Hospital Drive, 4401 Penn Ave, Pittsburgh, PA, 15224, USA.Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, One Children's Hospital Drive, 4401 Penn Ave, Pittsburgh, PA, 15224, USA.Department of Medicine, Pulmonary Diseases, Critical Care & Environmental Medicine, Tulane University School of Medicine, 1430 Tulane Ave. Mail code sl279, New Orleans, LA, 70112, USA. dpociask@tulane.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31416461

Citation

Hebert, K D., et al. "IL-22Ra1 Is Induced During Influenza Infection By Direct and Indirect TLR3 Induction of STAT1." Respiratory Research, vol. 20, no. 1, 2019, p. 184.
Hebert KD, Mclaughlin N, Zhang Z, et al. IL-22Ra1 is induced during influenza infection by direct and indirect TLR3 induction of STAT1. Respir Res. 2019;20(1):184.
Hebert, K. D., Mclaughlin, N., Zhang, Z., Cipriani, A., Alcorn, J. F., & Pociask, D. A. (2019). IL-22Ra1 is induced during influenza infection by direct and indirect TLR3 induction of STAT1. Respiratory Research, 20(1), p. 184. doi:10.1186/s12931-019-1153-4.
Hebert KD, et al. IL-22Ra1 Is Induced During Influenza Infection By Direct and Indirect TLR3 Induction of STAT1. Respir Res. 2019 Aug 15;20(1):184. PubMed PMID: 31416461.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-22Ra1 is induced during influenza infection by direct and indirect TLR3 induction of STAT1. AU - Hebert,K D, AU - Mclaughlin,N, AU - Zhang,Zhe, AU - Cipriani,A, AU - Alcorn,J F, AU - Pociask,D A, Y1 - 2019/08/15/ PY - 2019/02/05/received PY - 2019/08/05/accepted PY - 2019/8/17/entrez PY - 2019/8/17/pubmed PY - 2019/8/17/medline KW - IFNβ KW - IL-22 KW - IL-22Ra1 KW - Influenza KW - STAT1 KW - TLR3 SP - 184 EP - 184 JF - Respiratory research JO - Respir. Res. VL - 20 IS - 1 N2 - BACKGROUND: Influenza attacks the epithelium of the lung, causing cell death and disruption of the epithelial barrier leading to fluid buildup in the lung and impairment of gas exchange. Limited treatment options for severe influenza pneumonia prioritize the need for the discovery of effective therapies. IL-22 is a cytokine that promotes tissue integrity and has strong promise as a treatment option. While research has been focused on the cytokine itself, there is limited understanding of the regulation of the IL-22 receptor (IL-22Ra1) at the epithelial surface during infection. METHODS: IL-22Ra1 levels were measured by qRT-PCR, western blot and immunofluorescence following H1N1 influenza infection (A/PR/8/34 H1N1) or synthetic TLR3 mimetic, Poly (I:C). Regulation of the receptor was determined using STAT inhibitors (STAT1, STAT3 and PanSTAT inhibitors), TLR3 inhibition, and neutralization of interferon alpha receptor 2 (IFNAR2). Significance was determined by a p-value of greater than 0.05. Significance between two groups was measured using unpaired t-test and significance between more than two groups was measured using one-way ANOVA with Tukey Multiple Comparison Test. RESULTS: Here we show both in vivo and in vitro that IL-22Ra1 was induced as early as 24 h after influenza (H1N1 PR8) infection. This induction was triggered by toll-like receptor 3 (TLR3) as a TLR3 mimetic [Poly (I:C)] also induced IL-22Ra1 and inhibition of endosomal formation required for TLR3 function inhibited this process. This upregulation was dependent upon IFNβ signaling through STAT1. Importantly, induction of IL-22Ra1 significantly increased IL-22 signaling as evidenced by pSTAT3 levels following IL-22 treatment. CONCLUSION: Collectively, these data suggest epithelial cells may optimize the beneficial effects of IL-22 through the induction of the IL-22 receptor during viral infection in the lung. SN - 1465-993X UR - https://www.unboundmedicine.com/medline/citation/31416461/IL-22Ra1_is_induced_during_influenza_infection_by_direct_and_indirect_TLR3_induction_of_STAT1 L2 - https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-019-1153-4 DB - PRIME DP - Unbound Medicine ER -