Anti-FOXP3 monoclonal antibody, clone nBcdbn 33622

Bone morphogenic proteins (BMPs) are members of the transforming growth factor beta (TGF-beta) cytokine family promoting differentiation, homeostasis, and self-renewal of multiple tissues. We show that signaling through the bone morphogenic protein receptor 1 alpha (BMPR1 alpha) sustains expression of FOXP3 in T-reg cells in peripheral lymphoid tissues. BMPR1 alpha signaling promotes molecular circuits supporting acquisition and preservation of T-reg cell phenotype and inhibiting differentiation of pro-inflammatory effector Th1/Th17 CD4(+) T cell. Mechanistically, increased expression of KDM6B (JMJD3) histone demethylase, an antagonist of the polycomb repressive complex 2, underlies lineage-specific changes of T cell phenotypes associated with abrogation of BMPR1 alpha signaling. These results reveal that BMPs are immunoregulatory cytokines mediating maturation and stability of peripheral FOXP3(+) regulatory T cells (T-reg cells) and controlling generation of iT(reg) cells. Thus, we establish that BMPs, a large cytokine family, are an essential link between stromal tissues and the adaptive immune system involved in sustaining tissue homeostasis by promoting immunological tolerance.

The ectoenzymes CD39 and CD73 play a major role in controlling tissue inflammation by regulating the balance between adenosine triphosphate (ATP) and adenosine. Still, little is known about the role of these two enzymes and ATP and its metabolites in the pathophysiology of inflammatory bowel disease (IBD). We isolated mononuclear cells from peripheral blood and lamina propria of the large intestine of patients diagnosed with IBD and of healthy volunteers. We then comprehensively analyzed the CD39 and CD73 expression patterns together with markers of activation (HLA-DR, CD38), differentiation (CCR7, CD45RA) and tissue-residency (CD69, CD103, CD49a) on CD4(+), CD8(+), gamma delta T+ cells and mucosa-associated invariant T cells using flow cytometry. CD39 expression levels of gamma delta(+)and CD8(+)T cells in lamina propria lymphocytes (LPL) were much higher compared to peripheral blood mononuclear cells. Moreover, the frequency of CD39(+)CD4(+)and CD8(+), but not gamma delta+LPL positively correlated with T-cell activation. The frequency of CD39(+)cells among tissue-resident memory LPL (Trm) was higher compared to non-Trm for all subsets, confirming that CD39 is a marker for the tissue-resident memory phenotype. gamma delta(+)Trm also showed a distinct cytokine profile upon stimulation - the frequency of IFN-gamma(+)and IL-17A(+)cells was significantly lower in gamma delta(+)Trm compared to non-Trm. Interestingly, we observed a decreased frequency of CD39(+)gamma delta T+ cells in IBD patients compared to healthy controls (p= 0.0049). Prospective studies need to elucidate the exact role of this novel CD39(+)gamma delta T+-cell population with tissue-resident memory phenotype and its possible contribution to the pathogenesis of IBD and other inflammatory disorders.