Atopic dermatitis (AD) is a common disease affecting over 10% of children and adults, which severely impairs quality of life. Accumulating evidence has revealed that thymic stromal lymphopoietin (TSLP) of a pleiotropic cytokine play a critical role in the maintenance of AD. Currently, epidermal cells of AD are postulated as a major producer of TSLP, eventually leading to unfavorable local inflammation. However a property of the epidermal cells of AD is largely unknown. In the present study we assessed a functional significance of an epitheliotropic transcription factor p63 of a p53 homologue in the skin lesions of AD. Interestingly immunohistochemical analysis indicated constitutive downregulation of p63 of the epidermal cells in AD-affected skin areas. Further in vitro experiments using primary epidermal cells demonstrated that TSLP stimulation efficiently allowed cells to secrete TSLP as well as several inflammatory cytokines. Moreover it was found that the levels of expression of TSLP receptor (TSLPR) were under the control of p63. Collectively these indicate that the downregulation of p63 may cause chronic inflammation through providing a harmful TSLP-TSLPR axis to epidermal cells. Together with the evidence that innate ligands to TLRs like TLR3 could steadily suppress p63, our data would provide new insight into the pathogenesis of AD, especially with respect to the operation of innate immune responses by epidermal p63.
OSAS is attributable to periodic collapse of the upper airway due to adenotonsillar hypertrophy, featuring prominent germinal centers and wide interfollicular zones. However, the mechanism is still unclear. Here we present the possible involvement of Tfh cells in the pathogenesis of OSAS as indicated by comprehensive analysis of tonsillar lymphocytes of OSAS patients. The results revealed that tonsillar Tfh cells were plentiful in OSAS compared to recurrent tonsillitis (RT) without any discrepancy of T-cell components between the tonsils of OSAS and RT patients, indicating a ‘Tfh shift’ in OSAS tonsils. In addition, in vitro experiments delineated a unique function of the Tfh cells of OSAS, which could help expand the number of naive B cells and, more extensively, memory B cells, which allowed the Tfh cells to produce larger amounts of IL-4 and IFN-γ. Microarray studies newly identified transcripts characterizing the Tfh cells, including TIGIT and POU2AF1 regulating CXCR5 of B cells. Indeed, B-cell expansion was under the control of TIGIT, and large numbers of POU2AF1(+) Tfh cells were observed in and outside of germinal centers of OSAS tonsils. Overall these findings indicate that POU2AF1(+) Tfh cells cooperate with regional B-cell subsets to induce lymphoid hyperplasia.Focusing on the TIGIT-selective regulation of POU2AF1(+) Tfh cells, further investigations may provide a new modality for a noninvasive approach to treatment of this condition.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.