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Lymphotoxin alpha/beta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen
journal contributionposted on 2023-05-17, 07:44 authored by Ngo, VN, Heinrich KornerHeinrich Korner, Gunn, MD, Schmidt, KN, Riminton, DS, Cooper, MD, Browning, JL, Sedgwick, JD, Cyster, JG
Mice deficient in the cytokines tumor necrosis factor (TNF) or lymphotoxin (LT) Î±/Î² lack polarized B cell follicles in the spleen. Deficiency in CXC chemokine receptor 5 (CXCR5), a receptor for B lymphocyte chemoattractant (BLC), also causes loss of splenic follicles. Here we report that BLC expression by follicular stromal cells is defective in TNF-, TNF receptor 1 (TNFR1)-, LTÎ±- and LTÎ²-deficient mice. Treatment of adult mice with antagonists of LTÎ±1Î²2 also leads to decreased BLC expression. These findings indicate that LTÎ±1Î²2 and TNF have a role upstream of BLC/CXCR5 in the process of follicle formation. In addition to disrupted follicles, LT- deficient animals have disorganized T zones. Expression of the T cell attractant, secondary lymphoid tissue chemokine (SLC), by T zone stromal cells is found to be markedly depressed in LTÎ±-, and LTÎ²-deficient mice. Expression of the SLC-related chemokine, Epstein Barr virus-induced molecule 1 ligand chemokine (ELC), is also reduced. Exploring the basis for the reduced SLC expression led to identification of further disruptions in T zone stromal cells. Together these findings indicate that LTÎ±1Î²2 and TNF are required for the development and function of B and T zone stromal cells that make chemokines necessary for lymphocyte compartmentalization in the spleen.
Publication titleThe Journal of Experimental Medicine
Department/SchoolMenzies Institute for Medical Research
PublisherRockefeller Univ Press
Place of publication1114 First Ave, 4Th Fl, New York, USA, Ny, 10021