TSLP (Thymic Stromal Lymphopoietin)

Collectively, CLE exhibited potential as a natural anti-inflammatory agent by attenuating oxidative stress, downregulating inflammatory mediators, enhancing skin barrier function in vitro, and reducing ear edema in vivo.

In addition, anti-tumor ILC2s under the influence of the tumor microenvironment may become dysfunctional, ultimately resulting in tumor-progression. Understanding the specific cancer context and considering the similarities as well as the distinctive features of the two lymphoid type-2 cell subsets is essential for developing effective immunotherapeutic strategies by targeting the IL-1 and IL-33 cytokines.

Collectively, these findings demonstrate that IL-37 serves as a crucial immunomodulator in respiratory diseases, and targeting IL-37 offers novel insights and strategic opportunities for clinical intervention. This review systematically summarizes the molecular mechanisms of IL-37 and discusses its clinical therapeutic potential.

This study unveils a complex bidirectional relationship between circulating inflammatory factors and osteoporotic pathological fractures. These findings provide novel insights into the pathogenesis of osteoporosis and offer important clues for potential preventive, diagnostic, and therapeutic strategies.

Overall, we found a difference in inflammatory proteins negatively associated with thyroid cancer in the at- versus the pre-diagnosis group. These findings highlight that inflammation potentially has a dual role in thyroid carcinogenesis.

The interleukin (IL)-33/thymic stromal lymphopoietin (TSLP)/IL-7-induced growth of group 2 innate lymphoid cells (ILC2) in vitro was resistant to dexamethasone (DEX), but suppressed by everolimus, an mTOR inhibitor, in a concentration-dependent manner...The combination of the pan-class I phosphatidylinositide-3 kinase inhibitor, buparlisib and the pan-Akt inhibitor, capivasertib also attenuated the resistance of IL-33/TSLP/IL-7-exposed ILC2s to DEX...This study demonstrates that activation of the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (mTOR) pathway induces steroid resistance in group 2 innate lymphoid cells. Targeting mTOR with everolimus restores steroid sensitivity, highlighting mTOR inhibition as a promising pharmacotherapy for steroid-resistant asthma.

These cytokines are also implicated in non-T2 inflammation, particularly in refractory asthma phenotypes. Growing insights into epithelial cytokines and their complex signaling networks with the airway microenvironment have opened new avenues for developing targeted and personalized treatment in SA.

Using an ovalbumin (OVA)-induced mouse model of severe asthma, we demonstrated that (1) CDK4+ and CDK6+ cells were elevated by 4.0- and 4.5-fold, respectively, in the lungs; (2) treatment with the CDK4/6 inhibitor palbociclib reduced fibrosis and ILC2 expansion by 77% and 87%, respectively; (3) increased ILC2s in the lungs showed high gene expression levels of CDK4, CDK6, and profibrotic factors, including fibroblast growth factor 2, fibroblast growth factor 23, collagen (COL) 4A2, COL10A1, and COL18A1; (4) thymic stromal lymphopoietin stimulation enhanced CDK4/6 protein expression in ILC2s, leading to their proliferation; and (5) palbociclib significantly inhibited the proliferation of ILC2s, at least in part by suppressing retinoblastoma phosphorylation...SIGNIFICANCE STATEMENT: Although cell cycle regulators have been implicated in immune cell proliferation, their role in group 2 innate lymphoid cell-driven asthma pathogenesis remains unexplored. Here, we identified the cyclin-dependent kinase 4/6-group 2 innate lymphoid cell axis as a previously unrecognized driver of airway remodeling in severe asthma.

Looking ahead, we speculate on the future drug discovery landscape of this field with the likely emergence of small molecules drugs for a range of clinically validated cytokines like TSLP and TL1A. This evolution will be accelerated by the advent of novel modalities like extracellular degraders, oral peptide drugs and the development of next-generation biological drugs with multi-valency and improved delivery.

Plasma inflammatory proteins causally influence DLBCL risk, partially mediated by metabolites. This underscores metabolite pathways as potential targets for therapeutic intervention.

BTA promotes keratinocyte proliferation and reduces TGF-β-induced inflammatory and pruritus-associated mediators. These findings suggest that BTA may facilitate wound healing by promoting keratinocyte proliferation while simultaneously modulating inflammation and pruritic responses.

We will also discuss recent findings demonstrating that an anti-TSLP monoclonal antibody (mAb) can exert a protective effect in a mouse model of colorectal cancer. The recent approval of an anti-TSLP mAb for asthma treatment also emphasizes the urgent need for additional research on the role of TSLP, a Janus cytokine, in tumorigenesis.