Model of pathogenesis of psoriasis. Part 1. Systemic psoriatic process.

Review and analytical study of results of experimental and theoretical works on etiology and pathogenesis of psoriatic disease was conducted. Psoriasis is dermal implication of systemic psoriatic process (SPP). New model of pathogenesis (hereinafter Y-model) explaining results of clinical and laboratory experiments was formulated. According to Y-model there are two main factors: hyperpermeability of small intestine for bacterial products and colonization of its walls by Gram+ bacteria (incl. psoriagenic bacteria PsB) and Gram(-) TLR4-active bacteria. Inside SPP there is a vicious cycle which is supported by disturbance of production and-or circulation of bile acids. SPP central subprocess is PAMP-nemia, namely chronic kPAMP-load on blood phagocytes (neutrophiles, monocytes and dendritic cells). The load results in increase of blood kPAMP level. The major key PAMP (kPAMP) are LPS and PG (incl. PG-Y – peptidoglycan of psoriagenic bacteria). Chronically increased kPAMP-load possibly provides tolerization of some neutrophils Neu, monocytes Mo and dendritic cells DC in blood flow. Chemostatus of tolerized blood Neu-T in process of their aging changes similarly to chemostatus nonactivated Neu and, hence, they carry endocytosed content from blood flow into bone marrow. Chemostatuses of tolerized Mo-T and DC-T are similar to nonactivated ones. So they don’t bring endocytosed content to lymph nodes or spleen and remain in blood. Tolerized phagocytes degrade endocytosed fragments of bacterial products containing kPAMP slowly and incompletely. Tolerized phagocytes appeared to be (PG-Y)-carriers are named by R-phagocytes and are designated as Neu-R, Mo-R and DC-R. SPP severity predetermines possibility of psoriasis initialization and maintenance because Mo-R and DC-R along with normal Mo and DC participate in homeostatic and inflammatory renewal of pool of dermal macrophages and DC of non-resident origin. Mo-R and DC-R enter derma and they can transform to mature maDC-Y (in particular – to TipDC), presenting Y‑antigen to specific TL-Y. Local processes in derma and epidermis will be described in details in the second part of the monograph. The given book is the authorized translation of the book, published in Russian (ISBN 978-5-905504-01-3; edition r4.0)