B Cells Produce the Tissue-Protective Protein RELMα during Helminth Infection, which Inhibits IL-17 Expression and Limits Emphysema

Cell Rep. 2018 Dec 4;25(10):2775-2783.e3. doi: 10.1016/j.celrep.2018.11.038.


Emphysema results in destruction of alveolar walls and enlargement of lung airspaces and has been shown to develop during helminth infections through IL-4R-independent mechanisms. We examined whether interleukin 17A (IL-17A) may instead modulate development of emphysematous pathology in mice infected with the helminth parasite Nippostrongylus brasiliensis. We found that transient elevations in IL-17A shortly after helminth infection triggered subsequent emphysema that destroyed alveolar structures. Furthermore, lung B cells, activated through IL-4R signaling, inhibited early onset of emphysematous pathology. IL-10 and other regulatory cytokines typically associated with B regulatory cell function did not play a major role in this response. Instead, at early stages of the response, B cells produced high levels of the tissue-protective protein, Resistin-like molecule α (RELMα), which then downregulated IL-17A expression. These studies show that transient elevations in IL-17A trigger emphysema and reveal a helminth-induced immune regulatory mechanism that controls IL-17A and the severity of emphysema.

Keywords: B lymphocytes; IL-17; RELMα; emphysema; helminth.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Lung Injury / complications
  • Acute Lung Injury / immunology
  • Animals
  • Antibodies / pharmacology
  • B-Lymphocytes / metabolism*
  • Down-Regulation
  • Emphysema / immunology*
  • Emphysema / parasitology*
  • Immunity / drug effects
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Interleukin-17 / metabolism*
  • Lung / immunology
  • Lung / parasitology
  • Lung / pathology
  • Mice, Inbred BALB C
  • Nippostrongylus / physiology*
  • Phenotype
  • Receptors, Interleukin-4 / metabolism
  • Signal Transduction
  • Strongylida Infections / parasitology*


  • Antibodies
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-17
  • Receptors, Interleukin-4
  • Retnla protein, mouse