Th17 cells contribute to pulmonary fibrosis and inflammation during chronic kidney disease progression after acute ischemia

Purvi Mehrotra, Jason A. Collett, Susan J. Gunst, David P. Basile

Research output: Contribution to journalArticle

4 Scopus citations


Acute kidney injury (AKI) is associated with high mortality rates and predisposes development of chronic kidney disease (CKD). Distant organ damage, particularly in the lung, may contribute to mortality in AKI patients. Animal models of AKI demonstrate an increase in pulmonary infiltration of lymphocytes and reveal an acute compromise of lung function, but the chronic effects of AKI on pulmonary inflammation are unknown. We hypothesized that in response to renal ischemia/reperfusion (I/R), there is a persistent systemic increase in Th17 cells with potential effects on pulmonary structure and function. Renal I/R injury was performed on rats, and CKD progression was hastened by unilateral nephrectomy and exposure to 4.0% sodium diet between 35 and 63 days post-I/R. Th17 cells in peripheral blood showed a progressive increase up to 63 days after recovery from I/R injury. Infiltration of leukocytes including Th17 cells was also elevated in bronchiolar lavage (BAL) fluid 7 days after I/R and remained elevated for up to 63 days. Lung histology demonstrated an increase in alveolar cellularity and a significant increase in picrosirius red staining. Suppression of lymphocytes with mycophenolate mofetil (MMF) or an IL-17 antagonist significantly reduced Th17 cell infiltration and fibrosis in lung. In addition, tracheal smooth muscle contraction to acetylcholine was significantly enhanced 63-days after I/R relative to sham-operated controls. These data suggest that AKI is associated with a persistent increase in circulating and lung Th17 cells which may promote pulmonary fibrosis and the potential alteration in airway contractility.

Original languageEnglish (US)
Pages (from-to)R265-R273
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number2
StatePublished - Feb 2018


  • Inflammation
  • Ischemia reperfusion
  • Kidney
  • Lymphocyte
  • Trachea

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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