The connection between Netherton syndrome and overactivation of epidermal/dermal proteases, particularly Kallikrein 5 (KLK5) has been well established and it is expected that a KLK5 inhibitor would improve the dermal barrier and also reduce the pain and itch that afflict Netherton syndrome patients.
Netherton syndrome (NS) is a rare but severe type of ichthyosis characterized by atopy, allergies, and potentially lethal skin overdesquamation associated with highly elevated proteolytic activities in LEKTI-deficient epidermis.
The novel functional link between LEKTI and TG1 should be taken into account when considering the development of a targeted topical protein therapy for Netherton syndrome.
Genome wide genotyping data revealed a total of 16, 5 and 6 digenic interactions were detected under RS conditions in low yielding NILs of IR64, TDK1-Sub1 and Savitri respectively while no significant interaction was found in high yielding NILs under RS and NS conditions in any of the genetic backgrounds used in this study.
Identification of potent and selective KLK5 inhibitors would enable further exploration of the disease biology and could ultimately lead to a treatment for NS.
A 21-year-old man with Netherton syndrome underwent investigation of a persistently elevated serum alanine transaminase, detected on routine monitoring.
LEKTI is known to be an essential molecule for the epidermal skin barrier, as demonstrated by SPINK5 nonsense mutation, which results in Netherton syndrome.
Although striking upregulation of TH17 pathway genes (IL17F and IL36B/G) resembling that seen in patients with psoriasis was common to all patients with ichthyoses in a severity-related manner, patients with Netherton syndrome showed the greatest T-cell activation (inducible costimulator [ICOS]) and a broader immune phenotype with T<sub>H</sub>1/IFN-γ, OASL, and T<sub>H</sub>2/IL-4 receptor/IL-5 skewing, although less than seen in patients with AD (all P < .05).
Although striking upregulation of TH17 pathway genes (IL17F and IL36B/G) resembling that seen in patients with psoriasis was common to all patients with ichthyoses in a severity-related manner, patients with Netherton syndrome showed the greatest T-cell activation (inducible costimulator [ICOS]) and a broader immune phenotype with T<sub>H</sub>1/IFN-γ, OASL, and T<sub>H</sub>2/IL-4 receptor/IL-5 skewing, although less than seen in patients with AD (all P < .05).
Although striking upregulation of TH17 pathway genes (IL17F and IL36B/G) resembling that seen in patients with psoriasis was common to all patients with ichthyoses in a severity-related manner, patients with Netherton syndrome showed the greatest T-cell activation (inducible costimulator [ICOS]) and a broader immune phenotype with T<sub>H</sub>1/IFN-γ, OASL, and T<sub>H</sub>2/IL-4 receptor/IL-5 skewing, although less than seen in patients with AD (all P < .05).
Although striking upregulation of TH17 pathway genes (IL17F and IL36B/G) resembling that seen in patients with psoriasis was common to all patients with ichthyoses in a severity-related manner, patients with Netherton syndrome showed the greatest T-cell activation (inducible costimulator [ICOS]) and a broader immune phenotype with T<sub>H</sub>1/IFN-γ, OASL, and T<sub>H</sub>2/IL-4 receptor/IL-5 skewing, although less than seen in patients with AD (all P < .05).
Kallikrein-related peptidases KLK5, KLK7 and KLK14 are important proteases in skin desquamation and aberrant KLK activity is associated with inflammatory skin diseases such as Netherton syndrome but also with various serious forms of cancer.
Kallikrein-related peptidases KLK5, KLK7 and KLK14 are important proteases in skin desquamation and aberrant KLK activity is associated with inflammatory skin diseases such as Netherton syndrome but also with various serious forms of cancer.
Kallikrein-related peptidases KLK5, KLK7 and KLK14 are important proteases in skin desquamation and aberrant KLK activity is associated with inflammatory skin diseases such as Netherton syndrome but also with various serious forms of cancer.
Additionally, three aquaporin genes (AQPs) including two plasma membrane intrinsic protein genes (PlPIP1;2, PlPIP2;1) and one NOD26-like intrinsic protein gene (PlNIP) were isolated, PlPIP1;2, and PlPIP2;1 that were induced by NS treatment took common effects on maintaining the water balance of cut P. lactiflora flowers.
A total of 64 Sprague‑Dawley rats were randomly divided into the following four groups: Sham‑operated rats with normal saline (NS)‑treatment (n=16); anterior cruciate ligament transection with partial medial meniscectomy (ACLT + MMx) rats with NS‑treatment (n=16); sham‑operated rats treated with PTH 1‑34 (n=16); and ACLT + MMx rats treated with PTH 1‑34 (n=16).