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Oriss TB, Raundhal M, Morse C, et al. IRF5 distinguishes severe asthma in humans and drives Th1 phenotype and airway hyperreactivity in mice. JCI Insight. 2017;2(10)doi: 10.1172/jci.insight.91019.
Oriss, T. B., Raundhal, M., Morse, C., Huff, R. E., Das, S., Hannum, R., Gauthier, M. C., Scholl, K. L., Chakraborty, K., Nouraie, S. M., Wenzel, S. E., Ray, P., & Ray, A. (2017). IRF5 distinguishes severe asthma in humans and drives Th1 phenotype and airway hyperreactivity in mice. JCI insight, 2(10), . https://doi.org/10.1172/jci.insight.91019
Oriss, Timothy B, et al. "IRF5 distinguishes severe asthma in humans and drives Th1 phenotype and airway hyperreactivity in mice." JCI insight vol. 2,10 (2017). doi: https://doi.org/10.1172/jci.insight.91019
Oriss TB, Raundhal M, Morse C, Huff RE, Das S, Hannum R, Gauthier MC, Scholl KL, Chakraborty K, Nouraie SM, Wenzel SE, Ray P, Ray A. IRF5 distinguishes severe asthma in humans and drives Th1 phenotype and airway hyperreactivity in mice. JCI Insight. 2017 May 18;2(10). doi: 10.1172/jci.insight.91019. eCollection 2017 May 18. PMID: 28515358; PMCID: PMC5436536.
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JCI Insight. 2017 May 18;2(10). doi: 10.1172/jci.insight.91019. eCollection 2017 May 18.

IRF5 distinguishes severe asthma in humans and drives Th1 phenotype and airway hyperreactivity in mice.

JCI insight

Timothy B Oriss, Mahesh Raundhal, Christina Morse, Rachael E Huff, Sudipta Das, Rachel Hannum, Marc C Gauthier, Kathryn L Scholl, Krishnendu Chakraborty, Seyed M Nouraie, Sally E Wenzel, Prabir Ray, Anuradha Ray

Affiliations

  1. Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine.
  2. Department of Immunology, and.
  3. University of Pittsburgh Asthma Institute at University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

PMID: 28515358 PMCID: PMC5436536 DOI: 10.1172/jci.insight.91019

Abstract

Severe asthma (SA) is a significant problem both clinically and economically, given its poor response to corticosteroids (CS). We recently reported a complex type 1-dominated (IFN-γ-dominated) immune response in more than 50% of severe asthmatics despite high-dose CS treatment. Also, IFN-γ was found to be critical for increased airway hyperreactivity (AHR) in our model of SA. The transcription factor IRF5 expressed in M1 macrophages can induce a Th1/Th17 response in cocultured human T cells. Here we show markedly higher expression of IRF5 in bronchoalveolar lavage (BAL) cells of severe asthmatics as compared with that in cells from milder asthmatics or healthy controls. Using our SA mouse model, we demonstrate that lack of IRF5 in lymph node migratory DCs severely limits their ability to stimulate the generation of IFN-γ- and IL-17-producing CD4+ T cells and IRF5-/- mice subjected to the SA model displayed significantly lower IFN-γ and IL-17 responses, albeit showing a reciprocal increase in Th2 response. However, the absence of IRF5 rendered the mice responsive to CS with suppression of the heightened Th2 response. These data support the notion that IRF5 inhibition in combination with CS may be a viable approach to manage disease in a subset of severe asthmatics.

Keywords: Pulmonology

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