The Immunology & Inflammation (I&I) initiative of the Helmholtz Association of German Research Centers was launched in 2017 as a consortium of 23 groups to bridge the immunological expertise of all centers in the Helmholtz Research Field Health. The participating labs work to elucidate the intricate connection between developmental, tissue-specific and environmental cues driving immune cell differentiation, their link to organ pathogenesis, and the potential for innovative therapies. In addition to seeding individual and tandem group projects across centers, I&I built a framework of activities to foster scientific exchange at all levels and is committed to training the next generation of scientists in the field. This year, I&I has entered a new expansion phase, which is considerably extending its underlying network and research portfolio, thus effectively translating into a major Immunology cross-center program of the Helmholtz Association.