β7 Integrins and other cell adhesion molecules are differentially expressed and modulated by TNFβ in different lymphocyte populations

Abstract

To explore the role of β7 integrins subfamily and TNFβ in intestinal mucosal immunity and disease, we have examined the expression and modulation by TNFβ of β7 integrins and other cell adhesion molecules on mouse intestinal lymphocytes. Most of the small intestine intraepithelial lymphocytes (SIEL) and lamina propria lymphocytes (LPL) were M293 (β7) and M290 (αM290β7) positive, whereas only 10-20% of SIEL and ~50% of LPL were R1-2 (α4β1/α4β7) positive. Only the expression of the R1-2 integrin was downregulated by TNFβ on SIEL. In contrast, expression of R1-2 was unaffected and expression of M290 was partially downregulated by TNFβ on LPL. About 2-3% of spleen lymphocytes (SL) were M293, M290, and R1-2 positive, and on these cells expression of M290 (and M293) was strongly induced by TNFβ. CD45 expression was partially downregulated by TNFβ on SIEL, LPL, and SL, whereas the expression of ICAM-1 and CD45RB was upregulated by TNFβ only on SIEL. TNFβ strongly downregulated CD44 expression on SIEL, upregulated CD44 expression on LPL, and had no effect on CD44 on SL. These phenotypic differences and different responses to TNFβ modulation between SIEL, LPL, and SL may reflect differences in the microenvironments in which these cells reside and imply that SIEL and LPL may play different roles in intestinal immunity. Further, TNFβ may play an important role in regulating the function of β7 integrins and other cell adhesion molecules.