Phenotypic and functional characterization of intraepithelial and lamina propria inflammatory cell infiltrate in autoimmune enteropathy.
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1
Istituto Nazionale di Genetica Molecolare (INGM), Autoimmunity, Italy
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2
Università degli Studi di Milano, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Italy
Autoimmune enteropathy (AE) is a rare syndrome characterized by severe villous atrophy, lamina propria (LP) infiltration by T lymphocytes and increased intraepithelial lymphocytes (IEL).
We characterized phenotype and function of inflammatory cells obtained from duodenal biopsies at disease onset and after steroid therapy.
Biopsies' analysis revealed an extensive infiltration of IEL mainly expressing CD4-CD8+CD103+. These cells produced high amounts of IFN-γ and a relevant amount of them coexpressed IL-17. Steroid treatment reduced the number of IEL CD4-CD8+CD103+ as well as the amount of IFN-γ and IL-17. Within LP CD4+ T cells, we found the same proportion of CXCR3+ and CCR6+ and a relevant number of CXCR3+CCR6+ cells. LP CD4+ T cells expressed high levels of IFN-γ, IL-17 and IL-22, while CD8+ cells expressed mainly IFN-γ.
After therapy we observed an increased number of CXCR3+ and a decreased number of CCR6+ and CXCR3+CCR6+ cells. Nevertheless, the levels of IFN-γ were dramatically reduced while IL-17 and IL-22 were increased. Steroid treatment was not affecting CD8+ cytokine production. In LP we found two population of dendritic cells (DCs), one expressing cell myeloid marker CD11c and CD103, the other being CD11c- CX3CR1+. Steroid treatment induced an increase of CX3CR1+ DC and a decrease of CD11c+ CD103+ DC.
Our data demonstrated that active AE leads to a massive infiltration by CXCR3+, CCR6+ cells and activated CD8+ T cells in LP, which is reduced after steroid therapy.
These results could be relevant for the identification of novel therapeutic targets in patients with AE.
Keywords:
Autoimmunity,
Lamina propria inflammatory cells,
inflammatory cytokines,
Intraepithelial lymphocytes,
Dendritic Cells (DC)
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Adaptive Immunity
Citation:
Paroni
M,
Nizzoli
G,
Abrignani
S,
Geginat
J and
Caprioli
F
(2013). Phenotypic and functional characterization of intraepithelial and lamina propria inflammatory cell infiltrate in autoimmune enteropathy..
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.01175
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Received:
31 Jul 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Flavio Caprioli, Università degli Studi di Milano, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Milano, Milano, 20122, Italy, flavio.caprioli@unimi.it