Allergen-dependent solubilization of IL-13 receptor alpha2 reveals a novel mechanism to regulate allergy.
BACKGROUND
Allergic sensitization affects half of western populations and often precedes the development of allergic disorders including asthma. Despite the critical role of allergens in the pathogenesis of these disorders, little is known about how allergens modulate the immune response. IL-13 receptor alpha2 (IL-13Ralpha2) is a decoy receptor for IL-13.


OBJECTIVE
Although the existence of soluble IL-13Ralpha2 has been documented, the mechanisms underlying its generation are unknown. Many allergens possess protease activity; we investigated whether IL-13Ralpha2 is solubilized in response to allergen treatment.


METHODS
We evaluated the ability of allergens to solubilize IL-13Ralpha2 in vitro and in vivo and examined the effect on IL-13 signaling and responses.


RESULTS
We determined that treatment of cells with house dust mite (HDM) allergen or purified Dermatophagoides pteronyssinus or Dermatophagoides farinae, but not other allergens, resulted in release of soluble IL-13Ralpha2 that was biologically active and inhibited IL-13 signaling. Prolonged exposure to HDM or treatment with mold allergens resulted in IL-13Ralpha2 degradation. This was associated with increased IL-13 signaling. A single treatment of HDM in vivo resulted in release of IL-13Ralpha2 into the bronchoalveolar lavage (BAL) fluid. BAL fluid from humans also contained IL-13Ralpha2; BAL fluid from individuals with asthma contained less IL-13Ralpha2 than that from controls.


CONCLUSIONS
Allergen exposure can directly affect the level of soluble IL-13Ralpha2 in a way that affects IL-13 signaling and responses.


CONCLUSIONS
Soluble IL-13Ralpha2 may be an important biomarker of environmental allergen exposure and asthma.
Daines
Michael O
MO
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Chen
Weiguo
W
Tabata
Yasuhiro
Y
Walker
Bradley A
BA
Gibson
Aaron M
AM
Masino
J Alexander
JA
Warrier
Manoj R
MR
Daines
Cori L
CL
Wenzel
Sally E
SE
Hershey
Gurjit K Khurana
GK
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000378:metabolism; D015415:Biomarkers; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology*; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011480:Protease Inhibitors / Q000494:pharmacology; D039981:Pyroglyphidae / Q000276:immunology; D050800:STAT6 Transcription Factor / Q000502:physiology; D012995:Solubility
D000485:Allergens; D015415:Biomarkers; D053663:Interleukin-13 Receptor alpha2 Subunit; D011480:Protease Inhibitors; D050800:STAT6 Transcription Factor