TNF hampers intestinal tissue repair in colitis by restricting IL-22 bioavailability.

Successful treatment of chronic inflammatory diseases integrates both the cessation of inflammation and the induction of adequate tissue repair processes. Strikingly, targeting a single proinflammatory cytokine, tumor necrosis factor (TNF), induces both processes in a relevant cohort of inflammatory bowel disease (IBD) patients. However, the molecular mechanisms underlying intestinal repair following TNF blockade during IBD remain elusive.

Novel mouse model to study T cell-dependent IgA induction in vivo.

Commensal microbiota at the mucosal surfaces controls multiple aspects of body homeostasis. Therefore, regulation of microflora composition by the host is crucial, and one of the mechanisms driving microbiota diversity is the production of large quantities of immunoglobulin A (IgA) at the mucosal surfaces. However, mechanisms of IgA induction in the gut are not completely understood.

Cellular sources of pathogenic and protective TNF and experimental strategies based on utilization of TNF humanized mice.

Over the years, tumor necrosis factor (TNF) has been implicated in the pathogenesis of various inflammatory conditions and TNF antagonists are highly efficient in treatment of multiple autoimmune diseases. However, it has been shown that various cellular sources of TNF exhibit distinct and non-redundant functions that can be either deleterious or beneficial. This suggests that systemic TNF blockade, in addition to neutralization of pathogenic TNF, may abrogate its protective functions, resulting in adverse effects.

Nonredundant function of soluble LTα3 produced by innate lymphoid cells in intestinal homeostasis.

Immunoglobulin A (IgA) production at mucosal surfaces contributes to protection against pathogens and controls intestinal microbiota composition. However, mechanisms regulating IgA induction are not completely defined. We show that soluble lymphotoxin α (sLTα3) produced by RORγt(+) innate lymphoid cells (ILCs) controls T cell-dependent IgA induction in the lamina propria via regulation of T cell homing to the gut.

Regulation and migratory role of P-selectin ligands during intestinal inflammation.

Dendritic cells from mesenteric lymph nodes (MLN) can convert retinal to retinoic acid (RA), which promotes induction of the gut-specific homing receptor α4β7. In contrast, priming within peripheral lymph nodes leads to upregulation of E- and P-selectin ligands (E- and P-lig). Apart from its α4β7 promoting effect, RA was shown to suppress E- and P-lig induction in vitro.