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Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
Published on: September 26, 2013
Human peripheral lymphoid tissues contain autoimmune regulator-expressing dendritic cells
Pietro Luigi Poliani1, Kai Kisand, Veronica Marrella
1Department of Pathology, University of Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy.
Autoimmune regulator (AIRE) expressing cells in human peripheral tissues, like lymph nodes, may prevent autoimmunity. These cells, identified as activated dendritic cells, express tissue-restricted antigens and tolerogenic molecules.
Area of Science:
- Immunology
- Cell Biology
Background:
- Autoimmune regulator (AIRE) is crucial for central tolerance in the thymus by regulating tissue-restricted antigens (TSAs).
- Peripheral tolerance mechanisms are essential to control autoreactive T cells that escape thymic negative selection.
Purpose of the Study:
- To investigate the presence and characteristics of AIRE-expressing cells in human peripheral lymphoid tissues.
- To determine the potential tolerogenic function of these extrathymic AIRE+ cells.
Main Methods:
- Immunohistochemistry and flow cytometry were used to identify and characterize AIRE+ cells in human lymph nodes, tonsils, and gut-associated lymphoid tissue.
- Isolation and analysis of HLADRhigh/AIRE+ cells from mesenteric lymph nodes to assess TSA and tolerogenic molecule expression.
Main Results:
- AIRE-expressing cells were found in human peripheral lymphoid tissues (lymph nodes, tonsils, GALT) but not the spleen, with increased numbers in abdominal LNs postnatally.
- These extrathymic AIRE+ cells exhibited dendritic morphology, expressed HLADR, fascin, CD11c, S100, and activation markers (CD40, CD83, DC-LAMP, CCR7).
- Isolated HLADRhigh/AIRE+ cells expressed TSAs (insulin, CYP17A1, CYP21A2) and tolerogenic molecules (IL-10, IDO), suggesting a functional role.
Conclusions:
- AIRE+ cells in human peripheral lymphoid tissues represent a subset of activated interdigitating dendritic cells.
- These cells express TSAs and tolerogenic molecules, indicating a potential role in maintaining peripheral tolerance and preventing autoimmunity.
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