Signaling from cytokine receptors that affect TH1 responses

Receptors of the various cytokines although structurally diverse, can yet be grouped into four major families of receptor proteins. Most cytokines that function in the immune system bind to either the Class I or Class II receptor families. Two other important receptor families are the immunoglobulin superfamily receptor and the TNF receptor family. Members of these receptor families also have critical roles in the immune system. A common feature of all these receptor families is that they do not exhibit any intrinsic tyrosine kinase activity. Receptor signaling is initiated through recruitment of kinases and through recruitment of cytosolic proteins to the receptor. In this review we will examine receptor signaling pathways initiated from five receptors that are all involved in either initiating T helper-1 (Th1) responses, or in downregulating Th1 responses. The following receptors: Interleukin (IL)-12, Interferon (IFN), IL-4, IL-10, and Tumor necrosis factor (TNF)-alpha will be examined. Signaling initiated from IL-12, IFN-gamma and TNF-alpha are important for inducing Th1 responses, and on the other hand signaling from IL-4 and IL-10 receptors inhibit Th1 responses. We will also discuss human immunodeficiencies resulting from mutations in the genes that encode the Type I cytokine receptors.