459 Resident memory CD8 T cells in both lesional and non- lesional skin of psoriasis patients have a potential of producing IL-17

Abstract

Mast cells (MCs) are crucial cells in the development of various types of diseases, including allergy, atopic dermatitis and hair disorders. Corticotropin releasing hormone (CRH) plays a central role in the stress response by regulating the hypothalamic-pituitary-adrenal (HPA) axis. However, CRH and its receptors (CRHR) have been recently identified within the skin and reported to play important roles in local cutaneous HPA axis. MCs are also reported to act as CRH mediated stress sentinels in tissue. We have previously shown that CRH induces connective tissue type (CT)-MC degranulation and promotes maturation. Here, we investigated whether CRH can also affect mucosal type (M)-MC biology by using human nasal polyp organ culture. The expression of both CRH and CRHR was detected within nasal polyp samples by immunohistochemistry and RT-PCR. CRH treatment in the organ culture increased the expression of ACTH receptor as well as glucocorticosteroid receptor in situ. Kit or tryp-tase+ M-MCs of isolated nasal polyps was shown to express CRHR by double immunofluorescence. CRH treatment significantly increased tryptase+ M-MC number and induced degranulation in situ. This was partially abrogated by the co-administration of stem cell factor (SCF) neutralizing antibody and CRHR antagonist, antalarmin. Just as human hair follicles organ culture, CRH also increased SCF expression within the epithelium of organ cultured nasal polyp samples. In contrast to CT-MC, CRH treatment significantly increased tryptase+ M-MC proliferation in situ. Furthermore, the effect of CRH on M-MCs degranulation and number was partially diminished by CRHR gene knockdown in situ. These results indicate that CRH induces both cutaneous and mucosal type neuroinflammation by promoting MC activity and increasing the number of it and that blockade of SCF and CRHR might be a novel future target for treating stress-induced disorders including atopic dermatitis and asthma.