Role of group 2 innate lymphoid cells (ILC2) in SHARPIN-deficient mice

SHARPIN is a component of the linear ubiquitination assembly complex and a key regulator of NFkB and integrin signaling. SHARPIN-deficient mice develop a phenotype known as chronic proliferative dermatitis ( cpdm ), characterized by progressive epidermal hyperplasia, apoptosis of keratinocytes, cutaneous and systemic eosinophilic inflammation, and hypoplasia of secondary lymphoid organs. We recently reported that the cutaneous inflammation in SHARPIN-deficient mice ( Sharpin cpdm ) develops independently of B and T lymphocytes. We therefore sought to determine the role of innate lymphoid cells (ILCs) in the dermatitis of Sharpin cpdm mice. ILCs were identified as a discrete population of CD45 + Lin − CD90.2 hi cells in the skin and draining lymph nodes (LN) of wild type (WT) and Sharpin cpdm mice. The number of ILCs was markedly increased in Sharpin cpdm mice. The majority of cells were group 2 ILC (ILC2) as indicated by labeling for GATA3, IL5, and IL13. The skin of Sharpin cpdm mice had increased expression of Il33 and Tslp mRNA. To determine the role of IL33, double mutant mice were generated in which the receptor for IL33 (Il1lr1 also known as ST2) was deleted. Loss of IL33-signaling greatly reduced the number of ILCs and reduced the severity of the dermatitis. These experiments suggest that the dermatitis in Sharpin cpdm mice is driven by IL33-dependent ILC2. Supported by the NIH (AR049288).