PMID- 21190445 OWN - NLM STAT- MEDLINE DCOM- 20110927 LR - 20171116 IS - 1557-9077 (Electronic) IS - 1050-7256 (Linking) VI - 21 IP - 5 DP - 2011 May TI - Thyroid hormones influence human dendritic cells' phenotype, function, and subsets distribution. PG - 533-40 LID - 10.1089/thy.2010.0183 [doi] AB - BACKGROUND: Dendritic cells (DCs) are the most effective antigen-presenting cells and key regulators of immune response. The immunoregulatory properties of DCs strongly depend on the microenvironment in which DCs have been matured and activated. Thyroid hormones are an important part of this environment and regulate many vital processes including growth and cellular metabolism. The aim of the study was an analysis of the influence of thyroid hormones on blood DC subtypes ex vivo, including the surface expression of molecules involved in antigen presentation, costimulation, and maturation, as well as on functional properties of DCs in vitro. METHODS: Blood samples for the quantitative and phenotypic analysis of peripheral blood plasmacytoid and myeloid DC subtypes were collected from thyroidectomized patients at two time points: (i) at the time of the so-called stimulation with endogenous thyrotropin-a group of hypothyroid patients after l-thyroxine (L-T(4)) withdrawal (pretreatment group)-and (ii) after 2 months of L-T(4) administration for thyrotropin suppression-a posttreatment group. The phenotype of DCs including HLA-DR, costimulatory molecules (CD40, CD80, and CD86), and maturation marker CD83 was assessed by flow cytometry. The influence of isolated peripheral blood DCs on autologous peripheral blood mononuclear cell proliferation and cytokine secretion (interferon alpha, interleukin-12) under triiodothyronine (T(3)) deficiency or T(3) excess was investigated in culture experiments. RESULTS: The percentage of peripheral blood plasmacytoid and myeloid DCs was higher after L-T(4) administration when compared with the pretreatment group. Moreover, the expression of CD86 on both DC subtypes was higher in the L-T(4) treated than in the hypothyroid patients. In the in vitro experiments, T(3) stimulation increased CD86 expression on cultured DCs. The phenotypic difference was paralleled by enhanced ability of T(3)-stimulated DCs to activate interleukin-12 secretion and proliferation of autologous peripheral blood mononuclear cells (PBMLs) in coculture experiments. CONCLUSIONS: In the present study, we provide for the first time an evidence that the thyrometabolic status has an influence on the phenotype and function of human peripheral blood DCs. This observation may be of potential importance for the understanding of the pathogenesis of immune and endocrine disorders. FAU - Dedecjus, Marek AU - Dedecjus M AD - Department of General, Oncological, and Endocrine Surgery, Polish Mother's Memorial Hospital-Research Institute, Medical University of Lodz, Lodz, Poland. mdedecjus@wp.pl FAU - Stasiolek, Mariusz AU - Stasiolek M FAU - Brzezinski, Jan AU - Brzezinski J FAU - Selmaj, Krzysztof AU - Selmaj K FAU - Lewinski, Andrzej AU - Lewinski A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101229 PL - United States TA - Thyroid JT - Thyroid : official journal of the American Thyroid Association JID - 9104317 RN - 0 (B7-2 Antigen) RN - 0 (Cytokines) RN - 0 (Thyroid Hormones) RN - 9002-71-5 (Thyrotropin) RN - Q51BO43MG4 (Thyroxine) SB - IM MH - Adult MH - B7-2 Antigen/biosynthesis MH - Case-Control Studies MH - Cell Separation MH - Cytokines/metabolism MH - Dendritic Cells/metabolism/*pathology MH - Female MH - Flow Cytometry MH - Humans MH - Hypothyroidism/metabolism/pathology MH - Lymphocyte Subsets MH - Male MH - Middle Aged MH - Phenotype MH - Thyroid Gland/physiology MH - Thyroid Hormones/*metabolism MH - Thyrotropin/metabolism MH - Thyroxine/metabolism EDAT- 2010/12/31 06:00 MHDA- 2011/09/29 06:00 CRDT- 2010/12/31 06:00 PHST- 2010/12/31 06:00 [entrez] PHST- 2010/12/31 06:00 [pubmed] PHST- 2011/09/29 06:00 [medline] AID - 10.1089/thy.2010.0183 [doi] PST - ppublish SO - Thyroid. 2011 May;21(5):533-40. doi: 10.1089/thy.2010.0183. Epub 2010 Dec 29.