Megakaryocyte progenitors are the main APCs inducing Th17 response to lupus autoantigens and foreign antigens.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Hee-Kap KangSyamal K Datta

Abstract

In search of autoantigen-presenting cells that prime the pathogenic autoantibody-inducing Th cells of lupus, we found that CD41(+)CD151(+) cells among Lineage(-) (Lin(-)) CD117(+) (c-Kit(+)) CX3CR1(-) splenocytes depleted of known APCs were most proficient in presenting nuclear autoantigens from apoptotic cells to induce selectively an autoimmune Th17 response in different lupus-prone mouse strains. The new APCs have properties resembling megakaryocyte and/or bipotent megakaryocyte/erythroid progenitors of bone marrow, hence they are referred to as MM cells in this study. The MM cells produce requisite cytokines, but they require contact for optimal Th17 induction upon nucleosome feeding, and can induce Th17 only before undergoing differentiation to become c-Kit(-)CD41(+) cells. The MM cells expand up to 10-fold in peripheral blood of lupus patients and 49-fold in spleens of lupus mice preceding disease activity; they accelerate lupus in vivo and break tolerance in normal mice, inducing autoimmune Th17 cells. MM cells also cause Th17 skewing to foreign Ag in normal mice without Th17-polarizing culture conditions. Several molecules in MM cells are targets for blocking of autoimmunization. This study advances our understanding of...Continue Reading

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Citations

Jan 16, 2019·Journal of Leukocyte Biology·Pierre Cunin, Peter A Nigrovic
Jun 18, 2014·Pigment Cell & Melanoma Research·Jonathan M EbyI Caroline Le Poole
Jul 1, 2020·Platelets·Genevieve MarcouxEric Boilard
Nov 23, 2019·Platelets·Pierre Cunin, Peter A Nigrovic
May 28, 2019·Thrombosis Research·Genevieve Couldwell, Kellie R Machlus

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