Figure 7. A: CBM physiology CBM complexes are critical TCR signaling adapters. Antigen receptor stimulation leads to phosphorylation of CARD 11. Activated CARD 11 is recruited into the CBM complex to the ubiquitin regulatory proteins LUBAC and TRAF6 which ligate unique ubiquitin chains to BCL 10/MALT1 (not shown in Figure) and eventually lead to the activation of NFkB, JNK and ASCT2 regulating glutamine metabolism and activating MTOR. B: JAK1/STAT5/ TGFβ/STAT6 Physiology. TGFβ has roles in immune tolerance, cell cycle arrest, and wound healing. TGFβ signals through TGFBR1 and 2 Receptor. TGFβ increases IL4Rα expression and leads to T helper type 2 (TH2) differentiation and IgE production. ERBIN is a negative regulator of transforming growth factor (TGF)-signaling through interaction with SMAD proteins. STAT3 induces and then forms a complex with ERBIN. STAT5 is activated by signaling through receptors for various cytokines including IL2, hematopoietic growth factors, as well as growth hormone. STAT5B is an important regulator of FOXP3 expression, the essential TF for Tregs. STAT6 signaling induces activation of group 2 innate lymphoid cells (ILC2s), differentiation of TH2 cells from naïve CD4+ T cells and induction of T follicular helper (TFH) cells, which are crucial for B-cell affinity maturation and immunoglobulin class-switch recombination (CSR) in the germinal center. In non-immune cells, IL4/IL13 STAT6 is involved in collagen production of fibroblasts, the development of mucus-secreting goblet cells, eosinophil-attracting chemokine production from epithelial cells and induction of bronchial smooth muscle hyper-responsiveness.