Kimiko Nakajima1, Sayo Kataoka2, Kenji Sato3, Mikiro Takaishi3, Mayuko Yamamoto3, Hideki Nakajima3, Shigetoshi Sano3. 1. Department of Dermatology, Kochi Medical School, Kochi University, Kochi, Japan. Electronic address: nakajimk@kochi-u.ac.jp. 2. Science Research Center, Kochi Medical School, Kochi University, Kochi, Japan. 3. Department of Dermatology, Kochi Medical School, Kochi University, Kochi, Japan.
Abstract
BACKGROUND: Psoriasis is an inflammatory disease associated with aberrant crosstalk between the epidermis and immune system. However, the role of Langerhans cells (LCs) in psoriasis remains controversial. OBJECTIVES: To elucidate whether LCs are functionally involved in the development of psoriasis using a mouse model. METHODS: Two lines of transgenic mice were used and crossed. They included K5.Stat3C, the psoriasis-model mouse and langerin DTR knock-in (KI) mouse. We performed immunofluorescence staining for LCs in psoriatic lesion of human and model mice. Flow cytometric analyses were performed to compare between dendritic cells (DCs) and LCs in the epidermis and skin-draining lymph nodes (sDLNs). To assess cytokine/chemokine expression in the skin lesion or primary cultured keratinocytes, we performed RT-PCR, microarray analysis or intracellular staining on the flow cytometer. RESULTS: LCs were activated in psoriatic lesion of patients with psoriasis and K5.Stat3C mice. Compared with non-transgenic mice, K5.Stat3C mice constitutively showed an increased number of LCs in the sDLNs before psoriasis-like lesion developed. Stat3C transgenic keratinocytes expressed an elevated level of IL-1α. Psoriasis-like lesion in K5.Stat3C mice were attenuated in the absence of LCs, indicating that LCs were essential to the development of psoriasis-like lesion. Furthermore, we also recognized that epidermal LCs in psoriatic lesion of not only K5.Stat3C mice but also psoriasis patients produced IL-23. CONCLUSIONS: Our study suggests that Stat3 activation in keratinocytes may impact on LC activation in situ via IL-1α stimulation, at least in part, and that their presence may be essential for the pathogenesis of psoriasis through producing IL-23.
BACKGROUND:Psoriasis is an inflammatory disease associated with aberrant crosstalk between the epidermis and immune system. However, the role of Langerhans cells (LCs) in psoriasis remains controversial. OBJECTIVES: To elucidate whether LCs are functionally involved in the development of psoriasis using a mouse model. METHODS: Two lines of transgenic mice were used and crossed. They included K5.Stat3C, the psoriasis-model mouse and langerin DTR knock-in (KI) mouse. We performed immunofluorescence staining for LCs in psoriatic lesion of human and model mice. Flow cytometric analyses were performed to compare between dendritic cells (DCs) and LCs in the epidermis and skin-draining lymph nodes (sDLNs). To assess cytokine/chemokine expression in the skin lesion or primary cultured keratinocytes, we performed RT-PCR, microarray analysis or intracellular staining on the flow cytometer. RESULTS: LCs were activated in psoriatic lesion of patients with psoriasis and K5.Stat3C mice. Compared with non-transgenic mice, K5.Stat3C mice constitutively showed an increased number of LCs in the sDLNs before psoriasis-like lesion developed. Stat3C transgenic keratinocytes expressed an elevated level of IL-1α. Psoriasis-like lesion in K5.Stat3C mice were attenuated in the absence of LCs, indicating that LCs were essential to the development of psoriasis-like lesion. Furthermore, we also recognized that epidermal LCs in psoriatic lesion of not only K5.Stat3C mice but also psoriasispatients produced IL-23. CONCLUSIONS: Our study suggests that Stat3 activation in keratinocytes may impact on LC activation in situ via IL-1α stimulation, at least in part, and that their presence may be essential for the pathogenesis of psoriasis through producing IL-23.
Authors: Advaitaa Ravipati; Sabrina Nolan; Martin Alphonse; Dustin Dikeman; Christine Youn; Yu Wang; Nicholas Orlando; Garrett Patrick; Steven Lee; Roger V Ortines; Haiyun Liu; Robert J Miller; Carly A Dillen; Mark Marchitto; S Sarah Cai; Lloyd S Miller; Nathan K Archer Journal: J Invest Dermatol Date: 2021-10-07 Impact factor: 8.551
Authors: Alice Wang; Alexander L Fogel; Michael J Murphy; Gauri Panse; Meaghan K McGeary; Jennifer M McNiff; Marcus Bosenberg; Matthew D Vesely; Jeffrey M Cohen; Christine J Ko; Brett A King; William Damsky Journal: JID Innov Date: 2021-05-07