Immune cell function and differentiation are critically regulated by post-translational modifications (PTMs), which modulate protein activity, localization, and interactions. Recent advances have highlighted the importance of non-classical epigenetic modifications such as citrullination, lactylation, and palmitoylation in immune regulation. These modifications influence key processes including T cell activation, macrophage polarization, and antigen presentation, and are implicated in autoimmune diseases, cancer, and infectious disorders.

Importantly, emerging studies also suggest that these PTMs play critical roles in cardiovascular inflammation and tissue remodeling. For instance, macrophage lactylation has been linked to the resolution phase of inflammation and could influence the transition of cardiac-resident macrophages from pro-inflammatory to reparative phenotypes after myocardial injury. Citrullination has been detected in neutrophils and macrophages infiltrating ischemic heart tissue, potentially modulating their inflammatory potential. Meanwhile, palmitoylation has been shown to affect membrane localization and signaling of immune receptors such as TREM2, which is implicated in tumor-associated macrophage function and has been associated with chronic inflammation.

Understanding the molecular mechanisms and functional outcomes of these PTMs offers new avenues to manipulate immune cell plasticity in diverse pathological contexts, from chronic autoimmune diseases to cancer and cardiovascular disorders.

This Research Topic aims to compile cutting-edge research on the roles of understudied PTMs—particularly citrullination, lactylation, and palmitoylation—in immune cell function and disease. We seek to elucidate their molecular mechanisms, functional consequences, and therapeutic potential.

In addition to classical immune contexts, we particularly encourage studies exploring how these PTMs regulate macrophage and innate lymphoid cell (ILC) plasticity in inflamed tissues such as the heart, adipose depots, and tumor microenvironments. By bringing together multidisciplinary contributions spanning immunology, metabolism, and cardiovascular biology, we hope to foster a deeper understanding of how these modi-fications shape immune responses and to identify novel biomarkers and therapeutic tar-gets for immunotherapy and inflammatory disease treatment.

Ultimately, this collection seeks to bridge mechanistic insights and translational perspectives, highlighting epigenetic PTMs as powerful levers for rewiring immune responses in disease.

We welcome original research, reviews, and methodological articles that address, but are not limited to, the following themes:

• Mechanisms of citrullination, lactylation, and palmitoylation in immune cells

• Functional impacts on T cells, B cells, macrophages, dendritic cells, NK cells, and ILC subsets

• Roles in autoimmune diseases (e.g., RA, SLE), cardiovascular inflammation, cancer immunology, and infection

• Crosstalk between different PTMs and classical epigenetic mechanisms

• Interactions between PTMs and key immune regulators such as HMGB1 or TREM2

• Novel techniques for detecting and quantifying these modifications

• Therapeutic targeting of PTMs in immune-related diseases

Submissions integrating multi-omics or spatial transcriptomics approaches to dissect PTM-driven immune plasticity are especially encouraged.

Are you interested in contributing a manuscript to this Research Topic?

Post-translational modifications in immune regulation: mechanisms, plasticity, and therapeutic targets