How do lymph nodes develop? – An important transcription factor network in innate lymphoid cells has been deciphered

Lymph nodes are the central anatomical structures of the immune system: T and B cells are activated here to fight pathogens such as viruses and bacteria. However, in the case of rheumatic diseases, these cells can also be activated to react against self-antigens and  contribute to harmful inflammatory reactions because they mistakenly attack the body’s own structures. Lymph nodes thus play an extraordinarily important role both in immunity against pathogens as well as in chronic inflammatory diseases.

Lymph nodes are generated during embryogenesis by specialized cells termed lymphoid tissue inducer (LTi) cells. LTi cells express the transcription factor RORgt, which has been shown to be indispensable for their generation as RORgt-deficient mice do not develop LTi cells and thus lack LN. A new study by Christina Stehle and colleagues from Chiara Romagnani’s group at the DRFZ has now shown that not only RORgt is important, but rather a whole network of transcription factors also involving RORa and T-bet regulates the development of lymph nodes. This study, published in Nature Immunology, challenges our current understanding of the ontogeny of the immune system opening new avenues to modulate inflammatory responses during rheumatic diseases.