Airway epithelial cells initiate the allergen response through transglutaminase 2 by inducing IL-33 expression and a subsequent Th2 response.

Background: Transglutaminase 2 (TG2) is a post-translational protein-modifying enzyme that catalyzes the transamidation reaction, producing crosslinked or polyaminated proteins. Increased TG2 expression and activity have been reported in various inflammatory conditions, such as rheumatoid arthritis, inflammation-associated pulmonary fibrosis, and autoimmune encephalitis. In particular, TG2 from epithelial cells is important during the initial inflammatory response in the lung.

Transglutaminase 2 exacerbates experimental autoimmune encephalomyelitis through positive regulation of encephalitogenic T cell differentiation and inflammation.

The increased activity of transglutaminase 2 (TG2) in various inflammatory and fibrotic conditions results in the development of numerous disease processes. Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, is an inflammatory and demyelinating disease of the central nervous system and is mediated by many inflammatory cytokines and mediators. We examined the role of TG2 in encephalitogenic CD4(+) T cell responses and EAE development using mice lacking TG2 (TG2(-/-)).

Epithelial transglutaminase 2 is needed for T cell interleukin-17 production and subsequent pulmonary inflammation and fibrosis in bleomycin-treated mice.

Pulmonary fibrosis is a potentially life-threatening disease that may be caused by overt or asymptomatic inflammatory responses. However, the precise mechanisms by which tissue injury is translated into inflammation and consequent fibrosis remain to be established. Here, we show that in a lung injury model, bleomycin induced the secretion of IL-6 by epithelial cells in a transglutaminase 2 (TG2)-dependent manner.

Invariant NKT cells regulate experimental autoimmune uveitis through inhibition of Th17 differentiation.

Although NKT cells have been implicated in diverse immunomodulatory responses, the effector mechanisms underlying the NKT cell-mediated regulation of pathogenic T helper cells are not well understood. Here, we show that invariant NKT cells inhibited the differentiation of CD4(+) T cells into Th17 cells both in vitro and in vivo. The number of IL-17-producing CD4(+) T cells was reduced following co-culture with purified NK1.

CP-690550, a Janus kinase inhibitor, suppresses CD4+ T-cell-mediated acute graft-versus-host disease by inhibiting the interferon-γ pathway.

Background: Acute graft-versus-host disease (GVHD) is a critical obstacle to bone marrow transplantation. Although numerous studies have described immunosuppression protocols to mitigate acute GVHD, the need still exists for a more efficient immunosuppressant with fewer side effects. Here, we evaluated the protective effect of CP-690550, a newly developed Janus kinase inhibitor, in an acute GVHD model.