Somatostatin, dendritic cells and peptide T in psoriasis : a clinical, immunohistochemical and functional study

Peptide T is an octapeptide designed to block the CD4 receptor. In a phase 1 study 9 psoriasis patients were treated with 2 mg peptide T i.v. once daily for 28 days and followed for a further 3 months. Five patients improved their PASI score >50%. The clinical results were confirmed by assessments of the histopathological score and epidermal thickness on biopsies. Peptide T treatment caused an increase in CD1-positive dendritic cells and a decrease in infiltrating lymphocytes. Immunohistochemical analysis revealed major changes in a population of somatostatin-immunoreactive dendritic cells during the treatment.

Somatostatin is a neuropeptide that inhibits the release of several hormones. It also affects fundamental lymphocyte functions, such as proliferation and antibody production, and somatostatin has been used in several studies of psoriasis. We found more somatostatin- immunoreactive cells in psoriasis lesions than in normal skin. These cells did not co-express CD1a, CD35, CD45RB, CD45RO, CD68, factor XIIIa or S-100, and they probably represent a specific population of dendritic cells. A subgroup co-expressed HLA-DR, which suggests that these cells can present antigens to T-cells.

Changes in somatostatin- and factor XIIIa-immunoreactive dendritic cells in psoriatic skin were then studied in biopsies taken during treatment with clobetasol propionate or calcipotriol. We found a significant reduction in the number of somatostatin- and factor XIIIa-positive cells after both treatments. The rate of reduction in the somatostatin-positive cells differed between the groups and closely paralleled healing.

Most somatostatin-positive cells in psoriasis are found in the dermis. In view of the known effects of somatostatin on the immune system, these cells may regulate the function of surrounding lymphocytes. Somatostatin exerts its effects by binding to five distinct receptors (SSTR1-5). We used RT-PCR to map the mRNA expression of these receptors in normal blood T-lymphocytes and in eight leukemic T-cell lines. Normal T-cells, but not the leukemic T- cells, expressed mRNA for SSTR1 and SSTR 5. SSTR2, 3 and 4 were present in all the T-cells examined. SSTR5 was selectively expressed in activated normal T-cells. Normal T-lymphocytes and all the T-cell lines were negative with respect to somatostatin mRNA expression. Thus, although T-cells can respond to somatostatin, they do not seem to produce somatostatin themselves.

A prerequisite for the localization of T-lymphocytes in specific tissue sites, such as the skin, is that they can adhere specifically to endothelial cells and extracellular matrix (ECM) components. Somatostatin and somatostatin analogs specific for SSTR2 and/or SSTR3 enhanced the adhesion of T-cells to fibronectin, and to a certain extent also to collagen type IV and laminin. Thus, somatostatin regulates T-cell adhesion to ECM components via distinct receptor subtypes. Our findings indicate that somatostatin may be a major regulator of a fundamental lymphocyte function, the capacity of adhesion to ECM components. They also suggest that SSTR subtypes may be useful targets for therapy in disorders involving T-cells.

List of scientific papers

I. Marcusson JA, Talme T, Wetterberg L, Johansson O (1991). "Peptide T a new treatment for psoriasis? A study of nine patients" Acta Derm Venereol 71(6): 479-83
https://pubmed.ncbi.nlm.nih.gov/92142628

II. Talme T, Rozell BL, Sundqvist KG, Wetterberg L, Marcusson JA (1995). "Histopathological and immunohistochemical changes in psoriatic skin during peptide T treatment" Arch Dermatol Res 287(6): 553-7
https://pubmed.ncbi.nlm.nih.gov/96066109

III. Johansson O, Hilliges M, Talme T, Marcusson JA, Wetterberg L (1994). "Somatostatin immunoreactive cells in lesional psoriatic human skin during peptide T treatment" Acta Derm Venereol 74(2): 106-9
https://pubmed.ncbi.nlm.nih.gov/94270048

IV. Talme T, Schultzberg M, Sundqvist KG, Marcusson JA (1999). "Somatostatin- and factor XIIIa-immunoreactive cells in psoriasis during clobetasol propionate and calciprotriol treatment" Acta Derm Venereol 79(1): 44-8
https://pubmed.ncbi.nlm.nih.gov/99184662

V. Talme T, Schultzberg M, Sundqvist KG, Marcusson JA (1997). "Colocalization of somatostatin- and HLA-DR-like immunoreactivity in dendritic cells of psoriatic skin" Acta Derm Venereol 77(5): 338-42
https://pubmed.ncbi.nlm.nih.gov/97443262

VI. Talme T, Ivanoff J, Hägglund M, Ivanoff A, Van Neerven RJ, Sundqvist KG (2000). "Somatostatin receptor (SSTR) expression and function in normal and leukemic T-cells. Evidence for selective effects on adhesion to extra-cellular matrix components via SSTR2 and/or 3" (Submitted)