title: ICOS controls Foxp3(+) regulatory T-cell expansion, maintenance and IL-10 production during helminth infection.
abstract: Foxp3(+) regulatory T (Treg) cells are key immune regulators during helminth infections, and identifying the mechanisms governing their induction is of principal importance for the design of treatments for helminth infections, allergies and autoimmunity. Little is yet known regarding the co-stimulatory environment that favours the development of Foxp3(+) Treg-cell responses during helminth infections. As recent evidence implicates the co-stimulatory receptor ICOS in defining Foxp3(+) Treg-cell functions, we investigated the role of ICOS in helminth-induced Foxp3(+) Treg-cell responses. Infection of ICOS(-/-) mice with Heligmosomoides polygyrus or Schistosoma mansoni led to a reduced expansion and maintenance of Foxp3(+) Treg cells. Moreover, during H. polygyrus infection, ICOS deficiency resulted in increased Foxp3(+) Treg-cell apoptosis, a Foxp3(+) Treg-cell specific impairment in IL-10 production, and a failure to mount putatively adaptive Helios(-) Foxp3(+) Treg-cell responses within the intestinal lamina propria. Impaired lamina propria Foxp3(+) Treg-cell responses were associated with increased production of IL-4 and IL-13 by CD4(+) T cells, demonstrating that ICOS dominantly downregulates Type 2 responses at the infection site, sharply contrasting with its Type 2-promoting effects within lymphoid tissue. Thus, ICOS regulates Type 2 immunity in a tissue-specific manner, and plays a key role in driving Foxp3(+) Treg-cell expansion and function during helminth infections.
authors: Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
authors: Stephen A
authors: SA
authors: Redpath
authors: Nienke
authors: N
authors: van der Werf
authors: Ana M
authors: AM
authors: Cervera
authors: Andrew S
authors: AS
authors: MacDonald
authors: David
authors: D
authors: Gray
authors: Rick M
authors: RM
authors: Maizels
authors: Matthew D
authors: MD
authors: Taylor
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006373:Helminthiasis / Q000235:genetics* / Q000276:immunology*; D060889:Inducible T-Cell Co-Stimulator Protein / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000276:immunology / Q000469:parasitology; D009351:Nematospiroides dubius / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D016753:Interleukin-10