New therapeutic strategy for atopic dermatitis by targeting CHI3L1/ITGA5 axis

Atopic dermatitis (AD) a chronic inflammatory skin disease that is difficult to treat despite the dis-covery of various disease targets and development of ther-apeutics. Previous clinical studies have shown that chitinase 3-like protein 1 (CHI3L1), also known as YKL-40, associated the onset and severity of AD. 1–3 a autoim-mune Our CHI3L1 Previ-ously, we first inhibition of CHI3L1 by K284-6111, a novel CHI3L1 inhibitor, amelio-rates AD-like skin inflammation. 5 Here, we further investigated the role of CHI3L1 in AD pathogenesis and its underlying mechanism using CHI3L1 knockout (KO) mice and a CHI3L1-blocking antibody (CHI3L1-Ab), and based on out-comes, propose that a CHI3L1-targeted therapeutic strategy can be used to treat AD.

[1]  T. Bieber,et al.  Serum receptor activator of nuclear factor kappa‐Β ligand/osteoprotegerin ratio correlates with severity and suggests fracture's risk in older women with atopic dermatitis , 2021, Allergy.

[2]  J. Hong,et al.  Inhibition of Chitinase-3-like-1 by K284-6111 Reduces Atopic Skin Inflammation via Repressing Lactoferrin , 2021, Immune network.

[3]  Xiaoren Zhang,et al.  Chitinase-3 like-protein-1 function and its role in diseases , 2020, Signal Transduction and Targeted Therapy.

[4]  M. N. Kim,et al.  Chitinase 3‐like 1 drives allergic skin inflammation via Th2 immunity and M2 macrophage activation , 2019, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[5]  P. Korošec,et al.  SPINK5 is associated with early‐onset and CHI3L1 with late‐onset atopic dermatitis , 2017, International journal of immunogenetics.

[6]  J. Szepietowski,et al.  Chitinase-3-Like Protein 1 (YKL-40) Reflects the Severity of Symptoms in Atopic Dermatitis , 2017, Journal of immunology research.

[7]  Li Lin,et al.  Chitinase 3-like 1 induces survival and proliferation of intestinal epithelial cells during chronic inflammation and colitis-associated cancer by regulating S100A9 , 2015, Oncotarget.

[8]  Donald Gullberg,et al.  Integrins , 2009, Cell and Tissue Research.

[9]  R. Shao,et al.  YKL-40, a secreted glycoprotein, promotes tumor angiogenesis , 2009, Oncogene.

[10]  B. Imhof,et al.  Adhesion molecules in atopic dermatitis: upregulation of alpha6 integrin expression in spontaneous lesional skin as well as in atopen, antigen and irritative induced patch test reactions. , 1997, International archives of allergy and immunology.