Targeting Th2-typified immune responses to prevent immunopathology in rheumatic diseases: belittled therapeutic strategies?

Although Th2-associated immune responses have been well defined in atopic diseases and parasitic infections, their potential contribution to immunopathology in rheumatic diseases has scarcely been recognised. This is probably related to the clear predominance of Th1/Th17 over Th2 cells in a number of rheumatic diseases, such as rheumatoid arthritis (RA), psoriatic arthritis and primary Sjögren’s syndrome (pSS). Also, whereas a clear role for Th1/Th17 activity in immunopathology has been clearly demonstrated in these diseases, Th2-related phenomena such as IgE production are hardly detected. Indeed, Th2-associated atopic conditions and Th2 cytokines like interleukin (IL)-4 and IL-10 were shown to inhibit Th1-induced inflammatory responses in these diseases. 2 As a consequence the understanding of Th2-associated mediators, other than IL-4 and IgE, in these and other rheumatic conditions and the potential to target these have been underevaluated. However, recent data show that immune activation by typical Th2-associated pathways, such as mast cell activation and histamine-induced responses, or Th2-typified key regulatory molecules, such as thymic stromal lymphopoietin (TSLP), IL-33 and IL-13, contribute to inflammation and immunopathology in several rheumatic diseases.