This coupling between S100A8/A9 overproduction by myeloid cells in the context of disrupted GIP signaling and the impairment of whole-body energy homeostasis and type 2 immunity has immediate translational relevance, as elevated S100A8/A9 expression in VAT and serum is also detected in people with type 2 diabetes mellitus (T2DM) and obesity (48, 49). Here, IGKV1D-22 is linked to obesity due to melanocortin 4 receptor deficiency.