The T-cell immunoglobulin and mucin domain (Tim) gene family in asthma, allergy, and autoimmunity

Abstract

The T-cell immunoglobulin and mucin domain (Tim) gene family is a relatively newly discovered group of molecules with a conserved structure and important immunologic functions. Tim molecules express on many types of immune cells including T cells, B cells, dendritic cells, macrophages, and mast cells that have been shown to be involved in asthma, allergic rhinitis, food allergy, and autoimmunity. Tim-1-Tim-4 interaction promotes Th2 cytokine responses, and blocking this interaction can decrease airway inflammation in asthma and in allergic rhinitis. Tim-3 stimulates mast cells to produce Th2 cytokines, and anti-Tim-3 is able to dampen asthmatic inflammation. The Tim-3 ligand was shown to be greatly enhanced on intestinal epithelial cells in patients with food allergy and Tim-4 may play a role in maintaining oral tolerance and prevention of food allergy. Tim-3 deregulation plays a role in the pathogenesis of multiple sclerosis. Increased Tim-1 expression has been shown in mononuclear cells from systemic lupus erythematosus patients and Tim-3 may be involved in a protective role in rheumatoid arthritis.

Coeliac disease and asthma association in children: the role of antibiotic consumption

“…Therefore, vitamin D deficiency may be a common factor capable of increasing the risk of developing both coeliac disease and asthma. The possibility of a shared genetic basis should also be considered [25]. Moreover, as we based our definition of asthma on anti-asthmatic drug treatment, which is frequently prescribed to children for transient wheezing related to respiratory infections, we cannot discard the hypothesis that some infection related factor, rather than asthma, may lie at the basis of the association we describe herein.…”

Effects of Tim-3 silencing on the viability of fibroblast-like synoviocytes and lipopolysaccharide-induced inflammatory reactions

“…Tim-3 is also expressed on the surface of innate immune cells, including CD 4+ T cells, CD 8+ T cells, monocytes, B cells and natural killer cells (19). Typically, abnormalities of Tim-3 signaling pathway are associated with allergic, autoimmune and viral infectious diseases, including asthma, systemic lupus erythematosus, RA and aplastic anemia (16,17). Tim-3 potentially modulates the immune response by negatively regulating Th1 to inhibit the inflammatory reaction.…”

“…Cell viability was detected by MTT assay (Gibco; Thermo Fisher Scientific, Inc., Waltham, MA, USA) 48 h following transfection, as previously described (17). Purple formazan crystals were dissolved in dimethyl sulfoxide and absorbance was measured using a microplate reader (Thermo Fisher Scientific, Inc.) at a wavelength of 560 nm.…”

“…This gene family is located on human chromosome 5 and 3 different subtypes have been identified so far: Tim-1, Tim-2 and Tim-3 (15). Tim-3 is considered to be a specific surface marker of Th1 cells and is able to regulate the immune response of Th1 cells to participate in systemic lupus erythematosus, aplastic anemia and other autoimmune diseases (16,17). Furthermore, Tim-3 is highly expressed in cluster of differentiation (CD)4 + T cells, as well as the synovial tissue of patients with RA (17)(18)(19).…”

“…Tim-3 is considered to be a specific surface marker of Th1 cells and is able to regulate the immune response of Th1 cells to participate in systemic lupus erythematosus, aplastic anemia and other autoimmune diseases (16,17). Furthermore, Tim-3 is highly expressed in cluster of differentiation (CD)4 + T cells, as well as the synovial tissue of patients with RA (17)(18)(19). Tim-3 is closely associated with the TLR4 signaling pathway and participates in a variety of immune diseases by regulating this signaling pathway (20,21).…”