IL-13Rα2 has a protective role in a mouse model of cutaneous inflammation.
IL-13 is expressed in lesions of atopic dermatitis (AD) and has been associated with increased disease severity. IL-13 has two cognate receptors: IL-13Rα1 and IL-13Rα2. Although IL-13Rα2 expression is known to be induced in response to IL-13 in keratinocytes, its function in AD has never been evaluated. We characterized the loss of skin barrier function and the development of cutaneous inflammation in IL-13Rα2-null versus wild-type BALB/c mice following an epicutaneous allergen-sensitization/challenge model that shares similarities with human AD. Mice lacking IL-13Rα2 had significantly increased transepidermal water loss, cutaneous inflammation, peripheral eosinophilia, and IgG1 and IgE levels compared with wild-type mice. The rate of resolution of the cutaneous inflammation was not significantly altered in the IL-13Rα2-null mice. IL-13 induced expression of IL-13Rα2 in keratinocyte cell lines and primary human keratinocytes. Depletion of IL-13Rα2 in a keratinocyte cell line resulted in increased STAT6 signaling in response to IL-13. In conclusion, IL-13Rα2 serves a protective role in the pathogenesis of allergic inflammation and loss of skin barrier function in a mouse model of AD, suggesting that it may be an important endogenous regulator of IL-13-induced cutaneous inflammation in humans.
Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Umasundari
U
Sivaprasad
Manoj R
MR
Warrier
Aaron M
AM
Gibson
Weiguo
W
Chen
Yasuhiro
Y
Tabata
Stacey A
SA
Bass
Marc E
ME
Rothenberg
Gurjit K
GK
Khurana Hershey
D000818:Animals; D000831:Animals, Newborn; D002461:Cell Line, Transformed; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D003876:Dermatitis, Atopic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007231:Infant, Newborn; D018793:Interleukin-13 / Q000502:physiology; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D014870:Water Loss, Insensible / Q000276:immunology
C508598:IL4 protein, human; D018793:Interleukin-13; D053663:Interleukin-13 Receptor alpha2 Subunit; D015847:Interleukin-4