TNFAIP8L2 (TNF Alpha Induced Protein 8 Like 2)

Pan-lactylation levels in retinal tissue were assessed by Western Blot and markedly upregulated in adult TIPE2-/- retinas. These findings demonstrate that TIPE2 deficiency was associated with retina hypoperfusion and age-related retinal thinning, suggesting that TIPE2 plays an essential role in preserving the natural state of retina.

Rescue experiments with recombinant ubiquitin protein (Ub) and the ubiquitination inhibitor MG132 demonstrated that F-box and WD repeat protein 1A (FBW1A)-mediated ubiquitination of NLRP3 and C1qbp is required in TIPE2 deficiency-induced pyroptosis, mitochondrial damage and oxidative stress. Overexpression of TIPE2 suppressed NLRP3-mediated pyroptosis and C1qbp-mediated oxidative stress and improved respiratory function and pulmonary tissue damage in vivo. TIPE2 protects asthmatic bronchial epithelial cells from NLRP3-induced pyroptosis and C1qbp-induced oxidative stress by interacting with the E3 ubiquitin ligase FBW1A in vitro and in vivo.

TNFAIP8 family genes play distinct roles in AML pathogenesis and immune regulation. TNFAIP8L2 shows promise as a prognostic biomarker, while TNFAIP8 and TNFAIP8L1 may indicate adverse cytogenetic risk. The study highlights their potential as therapeutic targets in AML.

Additionally, the KEGG analysis demonstrated that TNFAIP8 family co-expressed genes are involved in regulating various pathways such as inflammatory mediator regulation of TRP channels, pathways in cancer, prolactin signaling pathway, and Fc gamma R-mediated phagocytosis. Overall, the findings suggest that TNFAIP8 family members may play a significant role in the development of glioma and have the potential to serve as prognostic indicators and therapeutic targets for individuals with glioma.

Notably, PIK3CG was expressed in B cells, while GGT5 and PTGIS were expressed in stromal cells. This study generates lipid metabolism-based signatures correlated with EMT, stemness and ICs for predicting prognosis of COAD, and provides potential therapeutic targets for immunotherapy in COAD.

At the same time, the integrity of the blood-milk barrier is compromised while inflammation is promoted, thereby reducing cell adhesion in the mammary glands. These findings contribute to a more comprehensive understanding of the metabolic status of mastitis and provide new insights into its impact on the immune system.

This review focuses on the structural characteristics, expression patterns, and functional roles of TIPE proteins, with a particular emphasis on the role and underlying mechanisms of TIPE2 in immune regulation and its involvement in different diseases. However, the current body of evidence is still limited in providing a comprehensive understanding of the complex role of TIPE2 in the human body, warranting further investigation to elucidate the possible mechanisms and functions of TIPE2 in diverse disease contexts.

Furthermore, TNFAIP8L2 controls differential activation of microglia and glucose metabolic reprogramming through the MAPK/mTOR/HIF-1α signaling axis. This study reveals that TNFAIP8L2 plays a critical role in neuropathic pain, providing important insights into glucose metabolic reprogramming and microglial phenotypic transition, which indicates that TNFAIP8L2 may be used as a potential drug target for the prevention of neuropathic pain.

Conclusions We present an advanced single cell dissection of blinatumomab-induced target-effector interaction, providing novel insights into the mechanism of action and TME dynamics to guide patient selection and next generation BiTEs. A larger patients' cohort and introduction of patients' cells to the PIC-seq in vitro model will be presented at the ASH.