According to the functional roles of the three essential factors TRPM8, Ig, and P-selectin, we can distinguish the progression of cold exposure–induced immunosuppression into three steps: step 1, the initiation of TRPM8-dependent RAAS-mediated hypertension; step 2, the elevation of circulating IgG levels; and step 3, the transmission of IVIg-like immunosuppressive signals (Figure 9). The gene discussed is SELP; the disease is Hypertension.