Cytotoxic Th1 and Th17 cells infiltrate the intestinal mucosa of Behcet patients and exhibit high levels of TNF-α in early phases of the disease

Giacomo Emmi, Elena Silvestri, Chiara Della Bella, Alessia Grassi, Marisa Benagiano, Fabio Cianchi, Danilo Squatrito, Luca Cantarini, Lorenzo Emmi, Carlo Selmi, Domenico Prisco, Mario Milco D'Elios

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background: Gastrointestinal involvement is one of the most serious in Behçet disease, potentially leading to severe complications. Aim of this study was to investigate at mucosal level the T-cell responses in Behçet patients with early intestinal involvement. Methods: We isolated T cells from intestinal mucosa of 8 patients with intestinal symptoms started within 6 months. T lymphocytes were cloned and analyzed for surface phenotype and cytokines production. Results:We obtained 382 T-cell clones: 324 were CD4+ and 58 were CD8+. Within the 324 CD4+ clones, 195 were able to secrete IFN-g and TNF-a, but not IL-4, nor IL-17 thus showing a polarized Th1 profile, whereas CD4 clones producing both IFN-g and IL-17 (Th1/Th17 profile) were 79. Likewise, the number of CD8 clones producing type 1 cytokines was higher than those of CD8 clones producing both type 1 and 2 cytokines. Almost all intestinal-derived T-cell clones expressed perforin-mediated cytotoxicity and Fas-Fas Ligand-mediated pro-apoptotic activity. Conclusions: Our results indicate that in the early stages of the disease, both Th1 and Th17 cells drive inflammation leading to mucosal damage via abnormal and long-lasting cytokines production as well as via both perforin-and Fas-Fas ligand-mediated cytotoxicity. Finally, all the T cells at mucosal level were able to produce large amount of TNF-a, suggesting that its production is a property of intestinal T cells of patients with early active intestinal disease. These results support the therapy with anti-TNF- A agents and suggest the use of anti-IL-17 monoclonal antibodies in Behçet patients with early intestinal involvement.

Original languageEnglish (US)
Pages (from-to)e5516
JournalMedicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries
Volume95
Issue number49
DOIs
StatePublished - 2016

Fingerprint

Th17 Cells
Th1 Cells
Intestinal Mucosa
T-Lymphocytes
Clone Cells
Interleukin-17
Cytokines
Perforin
Fas Ligand Protein
Intestinal Diseases
Interleukin-4
Monoclonal Antibodies
Inflammation
Phenotype

Keywords

  • Adalimumab
  • Behçet disease
  • Biological
  • Infliximab
  • Secukinumab
  • Th cells
  • Th17

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Cytotoxic Th1 and Th17 cells infiltrate the intestinal mucosa of Behcet patients and exhibit high levels of TNF-α in early phases of the disease. / Emmi, Giacomo; Silvestri, Elena; Bella, Chiara Della; Grassi, Alessia; Benagiano, Marisa; Cianchi, Fabio; Squatrito, Danilo; Cantarini, Luca; Emmi, Lorenzo; Selmi, Carlo; Prisco, Domenico; D'Elios, Mario Milco.

In: Medicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries, Vol. 95, No. 49, 2016, p. e5516.

Research output: Contribution to journalArticle

Emmi, Giacomo ; Silvestri, Elena ; Bella, Chiara Della ; Grassi, Alessia ; Benagiano, Marisa ; Cianchi, Fabio ; Squatrito, Danilo ; Cantarini, Luca ; Emmi, Lorenzo ; Selmi, Carlo ; Prisco, Domenico ; D'Elios, Mario Milco. / Cytotoxic Th1 and Th17 cells infiltrate the intestinal mucosa of Behcet patients and exhibit high levels of TNF-α in early phases of the disease. In: Medicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries. 2016 ; Vol. 95, No. 49. pp. e5516.
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T1 - Cytotoxic Th1 and Th17 cells infiltrate the intestinal mucosa of Behcet patients and exhibit high levels of TNF-α in early phases of the disease

AU - Emmi, Giacomo

AU - Silvestri, Elena

AU - Bella, Chiara Della

AU - Grassi, Alessia

AU - Benagiano, Marisa

AU - Cianchi, Fabio

AU - Squatrito, Danilo

AU - Cantarini, Luca

AU - Emmi, Lorenzo

AU - Selmi, Carlo

AU - Prisco, Domenico

AU - D'Elios, Mario Milco

PY - 2016

Y1 - 2016

N2 - Background: Gastrointestinal involvement is one of the most serious in Behçet disease, potentially leading to severe complications. Aim of this study was to investigate at mucosal level the T-cell responses in Behçet patients with early intestinal involvement. Methods: We isolated T cells from intestinal mucosa of 8 patients with intestinal symptoms started within 6 months. T lymphocytes were cloned and analyzed for surface phenotype and cytokines production. Results:We obtained 382 T-cell clones: 324 were CD4+ and 58 were CD8+. Within the 324 CD4+ clones, 195 were able to secrete IFN-g and TNF-a, but not IL-4, nor IL-17 thus showing a polarized Th1 profile, whereas CD4 clones producing both IFN-g and IL-17 (Th1/Th17 profile) were 79. Likewise, the number of CD8 clones producing type 1 cytokines was higher than those of CD8 clones producing both type 1 and 2 cytokines. Almost all intestinal-derived T-cell clones expressed perforin-mediated cytotoxicity and Fas-Fas Ligand-mediated pro-apoptotic activity. Conclusions: Our results indicate that in the early stages of the disease, both Th1 and Th17 cells drive inflammation leading to mucosal damage via abnormal and long-lasting cytokines production as well as via both perforin-and Fas-Fas ligand-mediated cytotoxicity. Finally, all the T cells at mucosal level were able to produce large amount of TNF-a, suggesting that its production is a property of intestinal T cells of patients with early active intestinal disease. These results support the therapy with anti-TNF- A agents and suggest the use of anti-IL-17 monoclonal antibodies in Behçet patients with early intestinal involvement.

AB - Background: Gastrointestinal involvement is one of the most serious in Behçet disease, potentially leading to severe complications. Aim of this study was to investigate at mucosal level the T-cell responses in Behçet patients with early intestinal involvement. Methods: We isolated T cells from intestinal mucosa of 8 patients with intestinal symptoms started within 6 months. T lymphocytes were cloned and analyzed for surface phenotype and cytokines production. Results:We obtained 382 T-cell clones: 324 were CD4+ and 58 were CD8+. Within the 324 CD4+ clones, 195 were able to secrete IFN-g and TNF-a, but not IL-4, nor IL-17 thus showing a polarized Th1 profile, whereas CD4 clones producing both IFN-g and IL-17 (Th1/Th17 profile) were 79. Likewise, the number of CD8 clones producing type 1 cytokines was higher than those of CD8 clones producing both type 1 and 2 cytokines. Almost all intestinal-derived T-cell clones expressed perforin-mediated cytotoxicity and Fas-Fas Ligand-mediated pro-apoptotic activity. Conclusions: Our results indicate that in the early stages of the disease, both Th1 and Th17 cells drive inflammation leading to mucosal damage via abnormal and long-lasting cytokines production as well as via both perforin-and Fas-Fas ligand-mediated cytotoxicity. Finally, all the T cells at mucosal level were able to produce large amount of TNF-a, suggesting that its production is a property of intestinal T cells of patients with early active intestinal disease. These results support the therapy with anti-TNF- A agents and suggest the use of anti-IL-17 monoclonal antibodies in Behçet patients with early intestinal involvement.

KW - Adalimumab

KW - Behçet disease

KW - Biological

KW - Infliximab

KW - Secukinumab

KW - Th cells

KW - Th17

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