Our research interest remains focused on cell trafficking in human physiology and pathology, with an emphasis on the mechanisms governing fine-tuning modulation of chemokine expression and activity, in order to identify novel therapeutic target for pharmacological intervention. Chemokines are secreted proteins, emerged as key controllers of cell migration. The effects of chemokines are mediated by seven transmembrane domain receptors that are differentially expressed in a wide range of cell types. The diversity of expression of the receptors and their reactivity to chemokines guarantee the correct tissue distribution of the different leukocytes under normal or pathological conditions.

Our group has described a mechanism regulating leukocyte migration, which shows how different molecules can induce cell responses to concentrations of chemokines that per se would be inactive, thus lowering their “migratory threshold”. To date there are still various aspects of this effect that we call “synergy” that we need to clarify, in view of having more effective therapies to promote the resolution inflammation, both in acute and chronic pathological conditions, such as in autoimmune diseases. During viral infections, such as in AIDS, we have demonstrated that the cells of the immune system has an altered response to stimuli, which are important for their recruitment into the organs that need their patrolling, such as the gut. A recent study on individuals recovered from COVID-19, carried out in collaboration with the groups of Davide Robbiani and Andrea Cavalli, has led to the discovery of anti-chemokine autoantibodies that are generated during infection, are maintained for months after infection, and are associated with protection from symptoms related to Long Covid.

Our studies on leukocyte trafficking in humans have led in 2024 to identify, in patients with Ankylosing Spondylitis, a population of T lymphocytes that are characterized by the expression of genes that promote ossification and that could represent a new therapeutic target to improve the therapy of this disease. Again in 2024 we have extended our research to the study of the interactions between alarmins and chemokines in tumors, and highlighted how this interaction can be important in the development of metastases.

These discoveries pave the way for the identification of new therapeutic targets in patients with acute or persistent infections, chronic inflammatory diseases and tumors, favoring the restoration of the functions of cell populations active in the immune response or inhibiting the excessive function of chemokines.

Valentina Cecchinato, PhD, Research associate – Over the last years, an independent line of research has been developed by Valentina Cecchinato. Her research focuses on understanding how alterations in the chemokine system could affect HIV-1 disease progression. HIV-1 infection, when left untreated, causes a gradual deterioration of the immune system, leading to the development of acquired immunodeficiency syndrome (AIDS). Although antiretroviral therapy is highly effective in treating the infection, it is unable to completely eradicate the virus, which evades the immune system’s control by hiding in various organs. Persistent alterations in the immune system and a state of chronic inflammation reduce the individual’s ability to effectively fight other diseases and respond appropriately to vaccines.

Recently, we have discovered the presence of autoantibodies against specific chemokines in people living with HIV. Our studies aim to determine how these autoantibodies contribute to disease progression—either by reducing chronic inflammation or, conversely, by impairing immune responses and thereby facilitating immune deficiency.

This research could pave the way for further preclinical studies aimed at evaluating the effectiveness of therapies targeting chemokines to reduce viral spread and restore immune responses during HIV infection.