The magnitude and duration of innate immune responses are regulated by a variety of inhibitory mechanisms that limit potential damage to tissues. Whereas the inflammatory response is critically important for protection against microbes, it has the potential to cause tissue injury and dis ease. Several mechanisms have evolved to provide a brake on inflammation, and these mechanisms come into play at the same time as or shortly after the initiation of inflammation. Furthermore, many of these control mechanisms are triggered by the same PAMPs and DAMPs that induce inflammation. We will describe a selected group of these regulatory mechanisms.

IL-10 is a cytokine that is produced by and inhibits activation of macrophages and DCs. IL-10 inhibits the production of various inflammatory cytokines by activated macrophages and DCs, including IL-1, TNF, and IL-12. Because it is both produced by macrophages and DCs and inhibits the functions of these cells, IL-10 is an example of a negative feedback regulator. Alternatively activated macrophages make more IL-10 than classically activated macrophages. IL-10 is produced by some nonhematopoietic cell types (e.g., keratinocytes). IL-10 is also produced by regulatory T cells. Loss-of-function mutations in the IL-10 receptor result in severe colitis that develops in infancy.

Macrophages produce a natural antagonist of IL-1 that is structurally homologous to the cytokine and binds to the same receptors but is biologically inactive, so that it functions as a competitive inhibitor of IL-1. It is therefore called IL-1 receptor antagonist (IL-1RA). Synthesis of IL-1RA is induced by many of the same stimuli that induce IL-1 production. Some studies in IL-1RA–deficient mice suggest that this inhibitory cytokine is required to prevent inflammatory diseases of joints and other tissues, and a rare disease caused by genetic deficiency of IL-1RA in humans is characterized by severe bone and skin inflammation. Recombinant IL-1RA was originally developed as a drug for the treatment of rheumatoid arthritis; it is an effective treatment for familial fever syndromes in which IL-1 production is dysregulated. Regulation of IL-1 mediated inflammation may also occur by expression of the type II receptor, which binds IL-1 but does not transduce an activating signal. The major function of this receptor may be to act as a decoy that competitively inhibits IL-1 binding to the type I signaling receptor.

There are numerous negative regulatory signaling path ways that block the activating signals generated by pat tern recognition receptors and inflammatory cytokines. Suppressors of cytokine signaling (SOCS) proteins are inhibitors of JAK-STAT signaling pathways linked to cytokine receptors. TLR signaling in macrophages and DCs induces the expression of SOCS proteins, which limit responses of these cells to exogenous cytokines such as type I IFNs. Proinflammatory responses of cells to TLR signaling are negatively regulated by SHP1, an intracellular protein phosphatase that inhibits numerous tyrosine kinase–dependent signaling pathways in lymphocytes. Many other examples of kinases and phosphatases inhibit TLR, NLR, and RLR signaling and small inhibitory RNAs that inhibit production of many of the mediators of innate immunity.

اخر الاخبار

اخبار العتبة العباسية المقدسة

أربعة محاور معرفية شهدتها منافساتُ الجولة الثانية من مسابقة (بصائر العلم)

مدارس الكفيل النسوية: مسابقة (بصائر العلم) مشروع تربوي حوزوي متكامل

بمشاركة 8 فرق.. انطلاق الجولة الثانية من مسابقة (بصائر العلم)

عبر وحدة الخدمة الإنسانية.. قسم حفظ النظام يقدّم خدماته لكبار السنّ من الزائرين

المزيد

الآخبار الصحية

طريقة مبتكرة للكشف المبكر عن أمراض القلب والشرايين

منظمة الصحة تحذر من خطر إدمان الشباب لأكياس النيكوتين

خبراء يحذرون من عادة شائعة تهدد صحة الملايين

خبير يكشف 5 حقائق طبية صادمة وغير معروفة

المزيد

الآخبار التكنلوجية

الأولى في العالم.. الصين تجري تجربة رائدة في الفضاء باستخدام "جنين اصطناعي"

دراسة حديثة تفند ربط التستوستيرون بالمخاطرة لدى الرجال

ميتا تضيف وضع "المحادثة المخفية" إلى تطبيق "واتساب"

فوبيا المرتفعات ليست من الدماغ.. دراسة تكشف السبب

المزيد

مواضيع ذات صلة

Stages of T-Cell Maturation

Stimulation of Adaptive Immunity

Systemic and Pathologic Consequences of Inflammation

Immuno microscopy

V(D)J Recombination

Role of Macrophages in Tissue Repair

Ingestion and Killing of Microbes by Activated Phagocytes

Sequence of Events in Inflammation: Vascular Changes and Leukocyte Migration Into Tissues

Double Antibody Sandwich ELISA (DAS ELISA)

Enzyme Immunosorbent Assays

Antibody Structure and Function

Apoptosis in the Immune System