Role of the phosphoinositide 3-kinase p110delta in generation of type 2 cytokine responses and allergic airway inflammation

Eur J Immunol. 2007 Feb;37(2):416-24. doi: 10.1002/eji.200636401.


Phosphoinositide 3-kinases (PI3K) regulate immune activation via their roles in signal transduction of multiple classes of receptors. Here, we examined the effect of genetic inactivation of the hemopoietic cell-restricted PI3K isoform p110delta on systemic cytokine and chemokine responses and allergic airway inflammation. We found that type 2 cytokine responses (IL-4, IL-5 and IL-13) are significantly decreased in p110delta mutants, whereas type 1 cytokine responses (IFN-gamma and CXCL10) were robust. Elevated IFN-gamma production during the primary response to ovalbumin (OVA) was associated with reduced production of the regulatory cytokine IL-10. IFN-gamma and IL-10 production normalized after secondary OVA immunization; however, type 2 cytokine production was persistently reduced. Type 2 cytokine-dependent airway inflammation elicited by intranasal challenge with OVA was dramatically reduced, with reduced levels of eosinophil recruitment and mucus production observed in the lungs. Induction of respiratory hyper-responsiveness to inhaled methacholine, a hallmark of asthma, was markedly attenuated in p110delta-inactivated mice. Adoptive transfer of OVA-primed splenocytes from normal but not p110delta-inactivated mice could induce airway eosinophilia in naive, airway-challenged recipient mice. These data demonstrate a novel functional role for p110delta signaling in induction of type 2 responses in vivo and may offer a new therapeutic target for Th2-mediated airway disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Phosphatidylinositol 4-Kinase / immunology*
  • 1-Phosphatidylinositol 4-Kinase / metabolism
  • Adoptive Transfer
  • Animals
  • Asthma / enzymology*
  • Asthma / immunology
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Inflammation / enzymology*
  • Inflammation / immunology
  • Isoenzymes / deficiency
  • Isoenzymes / immunology
  • Mice
  • Mice, Mutant Strains
  • Pulmonary Eosinophilia / enzymology
  • Pulmonary Eosinophilia / immunology
  • Respiratory Hypersensitivity / enzymology*
  • Respiratory Hypersensitivity / immunology


  • Cytokines
  • Isoenzymes
  • 1-Phosphatidylinositol 4-Kinase