Editorial: TGF-beta Superfamily Members in Immune Homeostasis and Disease

Natalie Eva Nieuwenhuizen^1*Ioannis Eleftherianos^2*Piotr Jan Kraj^3*Maria Semitekolou^4*

• ¹Julius Maximilian University of Würzburg, Würzburg, Western Cape, Germany
• ²The George Washington University, Washington, United States
• ³Old Dominion University, Norfolk, United States
• ⁴Idryma Iatrobiologikon Ereunon tes Akademias Athenon, Athens, Greece

The Transforming Growth Factor beta (TGF-beta) superfamily, encompassing molecules such as TGFs, activins, Bone Morphogenetic Proteins (BMPs), Growth/Differentiation Factor (GDFs) and Nodals, represents the largest family of growth and differentiation factors, playing crucial roles in developmental and physiological processes across animal species (1). These molecules are integral to tissue homeostasis and cell fate determination. Among them, TGF-beta is particularly noted for its regulatory influence on immune responses and tissue fibrosis (2,3). Recent research has expanded our understanding of the immune functions of other superfamily members, including activin A and BMPs (4). These molecules signal through receptor complexes composed of type I and II serine/threonine kinase receptors, which activate Smads and initiate transcription. The functional diversity of TGFbeta superfamily ligands is attributed to the varied combinations of receptor complexes and the interaction of Smads with numerous transcription factors and co-regulators (5). Despite growing evidence of their roles in immune responses, the involvement of these cytokines in diseases, especially infectious diseases, remains underexplored. This gap is partly due to the embryonic lethality of gene deletions and the challenges in detecting their roles through transcriptomic approaches (6). However, advancements in genetic technologies, such as CRISPR/Cas9 and specific inhibitors, offer promising avenues to uncover novel functions of these molecules (7). This research topic aimed to elucidate the roles of TGF-beta superfamily members in immune homeostasis and disease. The primary objectives included investigating the signaling pathways of these molecules, understanding their modulation of immune responses, and exploring their involvement in various diseases. Specific questions that were addressed included the mechanisms by which these cytokines influence immune responses and their potential roles in infectious diseases, autoimmunity, allergy, inflammation, and cancer as well as the potential therapeutic targeting of TGF-beta superfamily molecules.