IL-10 engages macrophages to shift Th17 cytokine dependency and pathogenicity during T cell-mediated colitis

نویسندگان

  • Bofeng Li
  • Prajwal Gurung
  • R. K. Subbarao Malireddi
  • Peter Vogel
  • Thirumala-Devi Kanneganti
  • Terrence L. Geiger
چکیده

Polymorphisms attenuating IL-10 signalling confer genetic risk for inflammatory bowel disease. Yet, how IL-10 prevents mucosal autoinflammation is incompletely understood. We demonstrate using lineage-specific deletions of IL-10Rα that IL-10 acts primarily through macrophages to limit colitis. Colitis depends on IL-6 to support pathologic Th17 cell generation in wild-type mice. However, specific ablation of macrophage IL-10Rα provokes excessive IL-1β production that overrides Th17 IL-6 dependency, amplifying the colonic Th17 response and disease severity. IL-10 not only inhibits pro-IL-1β production transcriptionally in macrophages, but suppresses caspase-1 activation and caspase-1-dependent maturation of pro-IL-1β to IL-1β. Therefore, lineage-specific effects of IL-10 skew the cytokine dependency of Th17 cell development required for colitis pathogenesis. Coordinated interventions may be needed to fully suppress Th17-mediated immunopathology.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

IL-10 Modulates Th17 Pathogenicity during Autoimmune Diseases

The immune system is essential for host defense against pathogen infections; however dysregulated immune response may lead to inflammatory or autoimmune diseases. Elevated activation of both innate immune cells and T cells such as Th17 cells are linked to many autoimmune diseases, including Multiple Sclerosis (MS), arthritis and inflammatory bowel disease (IBD). To keep immune homeostasis, the ...

متن کامل

Effects of T-2 Toxin on Cytokine Produc-tion by Mice Peritoneal Macrophages and Lymph Node T-Cells

Background: T-2 toxin is a mycotoxin of type A trichothecenes produced by several fungal genera such as Fusarium species. Mycotoxins can affect both cell mediated and humoral immune compartments. Objective: The purpose of this study was to investi-gate the effect of T-2 toxin on cytokine production by mouse peritoneal macrophages and lymph node T cells. Methods: Mouse peritoneal macrophages and...

متن کامل

JunB is essential for IL-23-dependent pathogenicity of Th17 cells

CD4+ T-helper cells producing interleukin-17 (IL-17), known as T-helper 17 (TH17) cells, comprise heterogeneous subsets that exhibit distinct pathogenicity. Although pathogenic and non-pathogenic TH17 subsets share a common RORγt-dependent TH17 transcriptional programme, transcriptional regulatory mechanisms specific to each of these subsets are mostly unknown. Here we show that the AP-1 transc...

متن کامل

Detection of IL-10 gene polymorphisms in patients with ulcerative colitis in Northern Iran

Background: Ulcerative colitis is a multifactorial disease in which the environmental and genetics factor are being involved together. Interleukins are a group of cytokine which are produced through T cells, monocytes, macrophages, and endothelial cells. Interleukin-10 is an important multitasking cytokine that has a key role in inflammatory responses. The promoter of interlekin-10 is highly po...

متن کامل

Biology of TH17 Lymphocytes, their Cytokines and Role in Disease

T lymphocytes that are involved in cellular mediated immunity include two types known as TCD8+ (Cytotoxic T lymphocytes) and TCD4+ (helper T lymphocytes). TCD4+ has four main subtypes, including TH1, TH2, TH17, and Treg Lymphocytes.TH17 lymphocytes play a role in defense against microbes that TH1 and TH2 lymphocytes have not the ability to respond to them. The most important cytokines, which ar...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2015