M2 macrophages secrete oncostatin M to facilitate pruritus in primary cutaneous amyloidosis

Summary: <font _mstmutation="1">Primary cutaneous amyloidosis (PCA) is a chronic dermatosis in which amyloid protein is deposited in the superficial dermis without involvement of other organs. Intense itching is a typical complication symptom in PCA.We sought to determine the specific pruritogenic cytokine and its related signal pathway in PCA lesions trough immunofluorescence and immunohistochemical staining. Inflammatory cells were detected by immunofluorescence and HE staining. To elucidated the correlation among inflammatory cells, pruritogenic cytokine and pruritus, we ask patients to self-evaluate their pruritus severity by NRS score.<br _mstmutation="1" /> Increased secretion of Oncostatin M (OSM) which was observed in PCA lesions had correlation with pruritus severity (r=0.6656, <i _mstmutation="1">P<0.05) while the generations of Interleukin-4, Interleukin-13, Interleukin-31 and Interleukin-33 are similar in healthy skin (<i _mstmutation="1">P<0.05). A number of macrophages (<i _mstmutation="1">P<0.001) and CD4<sup _mstmutation="1">+ T cells (<i _mstmutation="1">P<0.01) infiltrated in PCA lesions. Pruritus severity in PCA was correlated with the number of macrophages (r=0.7320, <i _mstmutation="1">P<0.05) rather than CD4<sup _mstmutation="1">+ T cells (r=0.2102, <i _mstmutation="1">P>0.05). In PCA, CD163<sup _mstmutation="1">+CD68<sup _mstmutation="1">+ M2 macrophages (77.28%±16.21%) are the major type of macrophages. OSM production in Primary cutaneous amyloidosis is largely secreted by macrophages. Dermal OSMRβ<sup _mstmutation="1">+ cells are increased (<i _mstmutation="1">P<0.05). Macrophages showed the activation of JAK-STAT, PI3K-AKT signal pathway. OSM appeared to induce pruritus in primary cutaneous amyloidosis lesions. It largely secreted by macrophages trough the activation of JAK-STAT, PI3K-AKT signal pathway.<br _mstmutation="1" /> </font> Kaixi Pan¹ 1. Guangdong Provincial Dermatology Hospital, Guangzhou, Guangdong, China. Translational Studies: Cell and Molecular Biology